Unraveling the complex roles of macrophages in obese adipose tissue: an overview

Chang Peng , Jun Chen , Rui Wu , Haowen Jiang , Jia Li

Front. Med. ›› 2024, Vol. 18 ›› Issue (2) : 205 -236.

PDF (3232KB)
Front. Med. ›› 2024, Vol. 18 ›› Issue (2) : 205 -236. DOI: 10.1007/s11684-023-1033-7
REVIEW

Unraveling the complex roles of macrophages in obese adipose tissue: an overview

Author information +
History +
PDF (3232KB)

Abstract

Macrophages, a heterogeneous population of innate immune cells, exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases. The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects, inducing insulin resistance through increased inflammation, impaired thermogenesis, and adipose tissue fibrosis. Meanwhile, adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis, facilitating the clearance of dead adipocytes, and promoting mitochondrial transfer. Exploring the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic interventions. Recently, the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell technology. In this review, we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity, as well as explore the potential of drug delivery systems targeting macrophages, aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.

Keywords

obesity / inflammation / adipose tissue macrophages / adipose tissue homeostasis

Cite this article

Download citation ▾
Chang Peng, Jun Chen, Rui Wu, Haowen Jiang, Jia Li. Unraveling the complex roles of macrophages in obese adipose tissue: an overview. Front. Med., 2024, 18(2): 205-236 DOI:10.1007/s11684-023-1033-7

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature 2000; 404(6778): 652–660

[2]

Lin S, Zhang A, Yuan L, Wang Y, Zhang C, Jiang J, Xu H, Yuan H, Yao H, Zhang Q, Zhang Y, Lou M, Wang P, Zhang ZN, Luan B. Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice. Nat Commun 2022; 13(1): 3301

[3]

Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol 2019; 15(5): 288–298

[4]

Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 2004; 89(6): 2595–2600

[5]

Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009; 9(1): 88

[6]

Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE. Why does obesity cause diabetes?. Cell Metab 2022; 34(1): 11–20

[7]

Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol 2012; 13(8): 707–712

[8]

Wang H, Liddell CA, Coates MM, Mooney MD, Levitz CE, Schumacher AE, Apfel H, Iannarone M, Phillips B, Lofgren KT, Sandar L, Dorrington RE, Rakovac I, Jacobs TA, Liang X, Zhou M, Zhu J, Yang G, Wang Y, Liu S, Li Y, Ozgoren AA, Abera SF, Abubakar I, Achoki T, Adelekan A, Ademi Z, Alemu ZA, Allen PJ, AlMazroa MA, Alvarez E, Amankwaa AA, Amare AT, Ammar W, Anwari P, Cunningham SA, Asad MM, Assadi R, Banerjee A, Basu S, Bedi N, Bekele T, Bell ML, Bhutta Z, Blore JD, Basara BB, Boufous S, Breitborde N, Bruce NG, Bui LN, Carapetis JR, Cárdenas R, Carpenter DO, Caso V, Castro RE, Catalá-Lopéz F, Cavlin A, Che X, Chiang PP, Chowdhury R, Christophi CA, Chuang TW, Cirillo M, da Costa Leite I, Courville KJ, Dandona L, Dandona R, Davis A, Dayama A, Deribe K, Dharmaratne SD, Dherani MK, Dilmen U, Ding EL, Edmond KM, Ermakov SP, Farzadfar F, Fereshtehnejad SM, Fijabi DO, Foigt N, Forouzanfar MH, Garcia AC, Geleijnse JM, Gessner BD, Goginashvili K, Gona P, Goto A, Gouda HN, Green MA, Greenwell KF, Gugnani HC, Gupta R, Hamadeh RR, Hammami M, Harb HL, Hay S, Hedayati MT, Hosgood HD, Hoy DG, Idrisov BT, Islami F, Ismayilova S, Jha V, Jiang G, Jonas JB, Juel K, Kabagambe EK, Kazi DS, Kengne AP, Kereselidze M, Khader YS, Khalifa SE, Khang YH, Kim D, Kinfu Y, Kinge JM, Kokubo Y, Kosen S, Defo BK, Kumar GA, Kumar K, Kumar RB, Lai T, Lan Q, Larsson A, Lee JT, Leinsalu M, Lim SS, Lipshultz SE, Logroscino G, Lotufo PA, Lunevicius R, Lyons RA, Ma S, Mahdi AA, Marzan MB, Mashal MT, Mazorodze TT, McGrath JJ, Memish ZA, Mendoza W, Mensah GA, Meretoja A, Miller TR, Mills EJ, Mohammad KA, Mokdad AH, Monasta L, Montico M, Moore AR, Moschandreas J, Msemburi WT, Mueller UO, Muszynska MM, Naghavi M, Naidoo KS, Narayan KM, Nejjari C, Ng M, de Dieu Ngirabega J, Nieuwenhuijsen MJ, Nyakarahuka L, Ohkubo T, Omer SB, Caicedo AJ, Pillay-van Wyk V, Pope D, Pourmalek F, Prabhakaran D, Rahman SU, Rana SM, Reilly RQ, Rojas-Rueda D, Ronfani L, Rushton L, Saeedi MY, Salomon JA, Sampson U, Santos IS, Sawhney M, Schmidt JC, Shakh-Nazarova M, She J, Sheikhbahaei S, Shibuya K, Shin HH, Shishani K, Shiue I, Sigfusdottir ID, Singh JA, Skirbekk V, Sliwa K, Soshnikov SS, Sposato LA, Stathopoulou VK, Stroumpoulis K, Tabb KM, Talongwa RT, Teixeira CM, Terkawi AS, Thomson AJ, Thorne-Lyman AL, Toyoshima H, Dimbuene ZT, Uwaliraye P, Uzun SB, Vasankari TJ, Vasconcelos AM, Vlassov VV, Vollset SE, Waller S, Wan X, Weichenthal S, Weiderpass E, Weintraub RG, Westerman R, Wilkinson JD, Williams HC, Yang YC, Yentur GK, Yip P, Yonemoto N, Younis M, Yu C, Jin KY, El Sayed Zaki M, Zhu S, Vos T, Lopez AD, Murray CJ. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384(9947): 957–979

[9]

CintiS. Obesity, Type 2 Diabetes and the Adipose Organ: A Pictorial Atlas from Research to Clinical Applications 1st ed. Springer, 2017

[10]

Cohen P, Kajimura S. The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol 2021; 22(6): 393–409

[11]

Abdullahi A, Jeschke MG. Taming the flames: targeting white adipose tissue browning in hypermetabolic conditions. Endocr Rev 2017; 38(6): 538–549

[12]

Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84(1): 277–359

[13]

Hildreth AD, Ma F, Wong YY, Sun R, Pellegrini M, O’Sullivan TE. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol 2021; 22(5): 639–653

[14]

Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014; 156(1–2): 20–44

[15]

Schipper HS, Prakken B, Kalkhoven E, Boes M. Adipose tissue-resident immune cells: key players in immunometabolism. Trends Endocrinol Metab 2012; 23(8): 407–415

[16]

Kojta I, Chacińska M, Błachnio-Zabielska A. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance. Nutrients 2020; 12(5): 1305

[17]

Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest 2011; 121(6): 2111–2117

[18]

Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature 2002; 420(6913): 333–336

[19]

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116(7): 1793–1801

[20]

Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 2007; 447(7148): 1116–1120

[21]

Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y, Tsuneyama K, Nagai Y, Takatsu K, Urakaze M, Kobayashi M, Tobe K. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 2009; 58(11): 2574–2582

[22]

Cildir G, Akıncılar SC, Tergaonkar V. Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol Med 2013; 19(8): 487–500

[23]

Chakarov S, Blériot C, Ginhoux F. Role of adipose tissue macrophages in obesity-related disorders. J Exp Med 2022; 219(7): e20211948

[24]

Lu X, Kong X, Wu H, Hao J, Li S, Gu Z, Zeng X, Shen Y, Wang S, Chen J, Fei X, Sun Y, Li X, Jiang L, Yang F, Wang J, Cai Z. UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders. Cell Metab 2023; 35(8): 1390–1405.e8

[25]

Dalmas E, Toubal A, Alzaid F, Blazek K, Eames HL, Lebozec K, Pini M, Hainault I, Montastier E, Denis RG, Ancel P, Lacombe A, Ling Y, Allatif O, Cruciani-Guglielmacci C, André S, Viguerie N, Poitou C, Stich V, Torcivia A, Foufelle F, Luquet S, Aron-Wisnewsky J, Langin D, Clément K, Udalova IA, Venteclef N. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat Med 2015; 21(6): 610–618

[26]

Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity. Diabetologia 2016; 59(5): 879–894

[27]

Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol (N Y) 2013; 9(9): 560–569

[28]

Wang J, Chen WD, Wang YD. The relationship between gut microbiota and inflammatory diseases: the role of macrophages. Front Microbiol 2020; 11: 1065

[29]

Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57(6): 1470–1481

[30]

Kim KA, Gu W, Lee IA, Joh EH, Kim DH. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 2012; 7(10): e47713

[31]

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112(12): 1796–1808

[32]

Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 2009; 458(7242): 1191–1195

[33]

Harford KA, Reynolds CM, McGillicuddy FC, Roche HM. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 2011; 70(4): 408–417

[34]

Jayashree B, Bibin YS, Prabhu D, Shanthirani CS, Gokulakrishnan K, Lakshmi BS, Mohan V, Balasubramanyam M. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem 2014; 388(1–2): 203–210

[35]

Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: a chronic low-grade inflammation and its markers. Cureus 2022; 14(2): e22711

[36]

Suganami T, Nishida J, Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 2005; 25(10): 2062–2068

[37]

Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 2012; 18(3): 363–374

[38]

Lancaster GI, Langley KG, Berglund NA, Kammoun HL, Reibe S, Estevez E, Weir J, Mellett NA, Pernes G, Conway JRW, Lee MKS, Timpson P, Murphy AJ, Masters SL, Gerondakis S, Bartonicek N, Kaczorowski DC, Dinger ME, Meikle PJ, Bond PJ, Febbraio MA. Evidence that TLR4 is not a receptor for saturated fatty acids but mediates lipid-induced inflammation by reprogramming macrophage metabolism. Cell Metab 2018; 27(5): 1096–1110.e5

[39]

Galic S, Fullerton MD, Schertzer JD, Sikkema S, Marcinko K, Walkley CR, Izon D, Honeyman J, Chen ZP, van Denderen BJ, Kemp BE, Steinberg GR. Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest 2011; 121(12): 4903–4915

[40]

Wang N, Tan HY, Li S, Wang D, Xu Y, Zhang C, Xia W, Che CM, Feng Y. SBP2 deficiency in adipose tissue macrophages drives insulin resistance in obesity. Sci Adv 2019; 5(8): eaav0198

[41]

Lee YS, Kim JW, Osborne O, Oh DY, Sasik R, Schenk S, Chen A, Chung H, Murphy A, Watkins SM, Quehenberger O, Johnson RS, Olefsky JM. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell 2014; 157(6): 1339–1352

[42]

Engin A. Adipose tissue hypoxia in obesity and its impact on preadipocytes and macrophages: hypoxia hypothesis. Adv Exp Med Biol 2017; 960: 305–326

[43]

Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007; 56(4): 901–911

[44]

Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 2007; 293(4): E1118–E1128

[45]

Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 2009; 58(3): 718–725

[46]

Sun K, Halberg N, Khan M, Magalang UJ, Scherer PE. Selective inhibition of hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction. Mol Cell Biol 2013; 33(5): 904–917

[47]

Seo JB, Riopel M, Cabrales P, Huh JY, Bandyopadhyay GK, Andreyev AY, Murphy AN, Beeman SC, Smith GI, Klein S, Lee YS, Olefsky JM. Knockdown of Ant2 reduces adipocyte hypoxia and improves insulin resistance in obesity. Nat Metab 2019; 1(1): 86–97

[48]

Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V. Cutting edge: essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J Immunol 2007; 178(12): 7516–7519

[49]

Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O’Neill LA. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 2013; 496(7444): 238–242

[50]

Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MA, Sheedy FJ, Gleeson LE, van den Bosch MW, Quinn SR, Domingo-Fernandez R, Johnston DG, Jiang JK, Israelsen WJ, Keane J, Thomas C, Clish C, Vander Heiden M, Xavier RJ, O’Neill LA. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab 2015; 21(1): 65–80

[51]

Li Y, Li YC, Liu XT, Zhang L, Chen YH, Zhao Q, Gao W, Liu B, Yang H, Li P. Blockage of citrate export prevents TCA cycle fragmentation via Irg1 inactivation. Cell Rep 2022; 38(7): 110391

[52]

Jansen HJ, Stienstra R, van Diepen JA, Hijmans A, van der Laak JA, Vervoort GM, Tack CJ. Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue. Diabetologia 2013; 56(12): 2573–2581

[53]

Pedersen DJ, Guilherme A, Danai LV, Heyda L, Matevossian A, Cohen J, Nicoloro SM, Straubhaar J, Noh HL, Jung D, Kim JK, Czech MP. A major role of insulin in promoting obesity-associated adipose tissue inflammation. Mol Metab 2015; 4(7): 507–518

[54]

Mauer J, Chaurasia B, Plum L, Quast T, Hampel B, Blüher M, Kolanus W, Kahn CR, Brüning JC. Myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance. PLoS Genet 2010; 6(5): e1000938

[55]

Klauder J, Henkel J, Vahrenbrink M, Wohlenberg AS, Camargo RG, Püschel GP. Direct and indirect modulation of LPS-induced cytokine production by insulin in human macrophages. Cytokine 2020; 136: 155241

[56]

Ratter JM, van Heck JIP, Rooijackers HMM, Jansen HJ, van Poppel PCM, Tack CJ, Stienstra R. Insulin acutely activates metabolism of primary human monocytes and promotes a proinflammatory phenotype. J Leukoc Biol 2021; 110(5): 885–891

[57]

Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM, Linn T. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review. Hum Reprod Update 2018; 24(1): 86–105

[58]

Geeraerts X, Bolli E, Fendt SM, Van Ginderachter JA. Macrophage metabolism as therapeutic target for cancer, atherosclerosis, and obesity. Front Immunol 2017; 8: 289

[59]

de Rekeneire N, Peila R, Ding J, Colbert LH, Visser M, Shorr RI, Kritchevsky SB, Kuller LH, Strotmeyer ES, Schwartz AV, Vellas B, Harris TB. Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study. Diabetes Care 2006; 29(8): 1902–1908

[60]

Venneri MA, Giannetta E, Panio G, De Gaetano R, Gianfrilli D, Pofi R, Masciarelli S, Fazi F, Pellegrini M, Lenzi A, Naro F, Isidori AM. Chronic inhibition of PDE5 limits pro-inflammatory monocyte-macrophage polarization in streptozotocin-induced diabetic mice. PLoS One 2015; 10(5): e0126580

[61]

Ren L. Protective effect of ganoderic acid against the streptozotocin induced diabetes, inflammation, hyperlipidemia and microbiota imbalance in diabetic rats. Saudi J Biol Sci 2019; 26(8): 1961–1972

[62]

Yapislar H, Haciosmanoglu E, Sarioglu T, Degirmencioglu S, Sogut I, Poteser M, Ekmekcioglu C. Anti-inflammatory effects of melatonin in rats with induced type 2 diabetes mellitus. Life (Basel) 2022; 12(4): 574

[63]

Lin Y, Berg AH, Iyengar P, Lam TK, Giacca A, Combs TP, Rajala MW, Du X, Rollman B, Li W, Hawkins M, Barzilai N, Rhodes CJ, Fantus IG, Brownlee M, Scherer PE. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 2005; 280(6): 4617–4626

[64]

Xu X, Qi X, Shao Y, Li Y, Fu X, Feng S, Wu Y. High glucose induced-macrophage activation through TGF-β-activated kinase 1 signaling pathway. Inflamm Res 2016; 65(8): 655–664

[65]

Huang SM, Wu CS, Chiu MH, Wu CH, Chang YT, Chen GS, Lan CE. High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNF-α: an important mechanism to delay the diabetic wound healing. J Dermatol Sci 2019; 96(3): 159–167

[66]

Paradkar PH, Mishra LS, Joshi JV, Dandekar SP, Vaidya RA, Vaidya AB. In vitro macrophage activation: a technique for screening anti-inflammatory, immunomodulatory and anticancer activity of phytomolecules. Indian J Exp Biol 2017; 55(3): 133–141

[67]

Van den Bossche J, O’Neill LA, Menon D. Macrophage immunometabolism: where are we (going)?. Trends Immunol 2017; 38(6): 395–406

[68]

Yan J, Horng T. Lipid metabolism in regulation of macrophage functions. Trends Cell Biol 2020; 30(12): 979–989

[69]

Jung SB, Choi MJ, Ryu D, Yi HS, Lee SE, Chang JY, Chung HK, Kim YK, Kang SG, Lee JH, Kim KS, Kim HJ, Kim CS, Lee CH, Williams RW, Kim H, Lee HK, Auwerx J, Shong M. Reduced oxidative capacity in macrophages results in systemic insulin resistance. Nat Commun 2018; 9(1): 1551

[70]

Wang Y, Tang B, Long L, Luo P, Xiang W, Li X, Wang H, Jiang Q, Tan X, Luo S, Li H, Wang Z, Chen Z, Leng Y, Jiang Z, Wang Y, Ma L, Wang R, Zeng C, Liu Z, Wang Y, Miao H, Shi C. Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages. Nat Commun 2021; 12(1): 102

[71]

Day EA, Ford RJ, Steinberg GR. AMPK as a therapeutic target for treating metabolic diseases. Trends Endocrinol Metab 2017; 28(8): 545–560

[72]

Moon JS, da Cunha FF, Huh JY, Andreyev AY, Lee J, Mahata SK, Reis FC, Nasamran CA, Lee YS. ANT2 drives proinflammatory macrophage activation in obesity. JCI Insight 2021; 6(20): e147033

[73]

Huang LH, Melton EM, Li H, Sohn P, Jung D, Tsai CY, Ma T, Sano H, Ha H, Friedline RH, Kim JK, Usherwood E, Chang CCY, Chang TY. Myeloid-specific Acat1 ablation attenuates inflammatory responses in macrophages, improves insulin sensitivity, and suppresses diet-induced obesity. Am J Physiol Endocrinol Metab 2018; 315(3): E340–E356

[74]

Petkevicius K, Virtue S, Bidault G, Jenkins B, Çubuk C, Morgantini C, Aouadi M, Dopazo J, Serlie MJ, Koulman A, Vidal-Puig A. Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity. Elife 2019; 8: e47990

[75]

Takei A, Nagashima S, Takei S, Yamamuro D, Murakami A, Wakabayashi T, Isoda M, Yamazaki H, Ebihara C, Takahashi M, Ebihara K, Ishibashi S. Myeloid HMG-CoA reductase determines adipose tissue inflammation, insulin resistance, and hepatic steatosis in diet-induced obese mice. Diabetes 2020; 69(2): 158–164

[76]

Sharma M, Boytard L, Hadi T, Koelwyn G, Simon R, Ouimet M, Seifert L, Spiro W, Yan B, Hutchison S, Fisher EA, Ramasamy R, Ramkhelawon B, Moore KJ. Enhanced glycolysis and HIF-1α activation in adipose tissue macrophages sustains local and systemic interleukin-1β production in obesity. Sci Rep 2020; 10(1): 5555

[77]

Yu W, Wang Z, Zhang K, Chi Z, Xu T, Jiang D, Chen S, Li W, Yang X, Zhang X, Wu Y, Wang D. One-carbon metabolism supports S-adenosylmethionine and histone methylation to drive inflammatory macrophages. Mol Cell 2019; 75(6): 1147–1160.e5

[78]

Liu PS, Wang H, Li X, Chao T, Teav T, Christen S, Di Conza G, Cheng WC, Chou CH, Vavakova M, Muret C, Debackere K, Mazzone M, Huang HD, Fendt SM, Ivanisevic J, Ho PC. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol 2017; 18(9): 985–994

[79]

Ran L, Zhang S, Wang G, Zhao P, Sun J, Zhou J, Gan H, Jeon R, Li Q, Herrmann J, Wang F. Mitochondrial pyruvate carrier-mediated metabolism is dispensable for the classical activation of macrophages. Nat Metab 2023; 5(5): 804–820

[80]

Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 2020; 11(1): 102

[81]

Rodriguez AE, Ducker GS, Billingham LK, Martinez CA, Mainolfi N, Suri V, Friedman A, Manfredi MG, Weinberg SE, Rabinowitz JD, Chandel NS. Serine metabolism supports macrophage IL-1β production. Cell Metab 2019; 29(4): 1003–1011.e4

[82]

McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 2010; 330(6002): 362–366

[83]

Wilhelm K, Ganesan J, Müller T, Dürr C, Grimm M, Beilhack A, Krempl CD, Sorichter S, Gerlach UV, Jüttner E, Zerweck A, Gärtner F, Pellegatti P, Di Virgilio F, Ferrari D, Kambham N, Fisch P, Finke J, Idzko M, Zeiser R. Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nat Med 2010; 16(12): 1434–1438

[84]

Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009; 461(7261): 282–286

[85]

Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010; 140(6): 900–917

[86]

Hetz C, Papa FR. The unfolded protein response and cell fate control. Mol Cell 2018; 69(2): 169–181

[87]

Hetz C, Martinon F, Rodriguez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1α. Physiol Rev 2011; 91(4): 1219–1243

[88]

Shan B, Wang X, Wu Y, Xu C, Xia Z, Dai J, Shao M, Zhao F, He S, Yang L, Zhang M, Nan F, Li J, Liu J, Liu J, Jia W, Qiu Y, Song B, Han JJ, Rui L, Duan SZ, Liu Y. The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity. Nat Immunol 2017; 18(5): 519–529

[89]

Kim JH, Lee E, Friedline RH, Suk S, Jung DY, Dagdeviren S, Hu X, Inashima K, Noh HL, Kwon JY, Nambu A, Huh JR, Han MS, Davis RJ, Lee AS, Lee KW, Kim JK. Endoplasmic reticulum chaperone GRP78 regulates macrophage function and insulin resistance in diet-induced obesity. FASEB J 2018; 32(4): 2292–2304

[90]

Song L, Kim DS, Gou W, Wang J, Wang P, Wei Z, Liu B, Li Z, Gou K, Wang H. GRP94 regulates M1 macrophage polarization and insulin resistance. Am J Physiol Endocrinol Metab 2020; 318(6): E1004–E1013

[91]

Li W, Wu H, Sui S, Wang Q, Xu S, Pang D. Targeting histone modifications in breast cancer: a precise weapon on the way. Front Cell Dev Biol 2021; 9: 736935

[92]

Chen L, Zhang J, Zou Y, Wang F, Li J, Sun F, Luo X, Zhang M, Guo Y, Yu Q, Yang P, Zhou Q, Chen Z, Zhang H, Gong Q, Zhao J, Eizirik DL, Zhou Z, Xiong F, Zhang S, Wang CY. Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus. Cell Death Differ 2021; 28(6): 1880–1899

[93]

Chen J, Xu X, Li Y, Li F, Zhang J, Xu Q, Chen W, Wei Y, Wang X. Kdm6a suppresses the alternative activation of macrophages and impairs energy expenditure in obesity. Cell Death Differ 2021; 28(5): 1688–1704

[94]

Chi Z, Chen S, Xu T, Zhen W, Yu W, Jiang D, Guo X, Wang Z, Zhang K, Li M, Zhang J, Fang H, Yang D, Ye Q, Yang X, Lin H, Yang F, Zhang X, Wang D. Histone deacetylase 3 couples mitochondria to drive IL-1β-dependent inflammation by configuring fatty acid oxidation. Mol Cell 2020; 80(1): 43–58.e7

[95]

Kang H, Lee Y, Kim MB, Hu S, Jang H, Park YK, Lee JY. The loss of histone deacetylase 4 in macrophages exacerbates hepatic and adipose tissue inflammation in male but not in female mice with diet-induced non-alcoholic steatohepatitis. J Pathol 2021; 255(3): 319–329

[96]

Lee Y, Ka SO, Cha HN, Chae YN, Kim MK, Park SY, Bae EJ, Park BH. Myeloid sirtuin 6 deficiency causes insulin resistance in high-fat diet-fed mice by eliciting macrophage polarization toward an M1 phenotype. Diabetes 2017; 66(10): 2659–2668

[97]

Zhou Q, Wang Y, Lu Z, Wang B, Li L, You M, Wang L, Cao T, Zhao Y, Li Q, Mou A, Shu W, He H, Zhao Z, Liu D, Zhu Z, Gao P, Yan Z. Mitochondrial dysfunction caused by SIRT3 inhibition drives proinflammatory macrophage polarization in obesity. Obesity (Silver Spring) 2023; 31(4): 1050–1063

[98]

Keiran N, Ceperuelo-Mallafré V, Calvo E, Hernández-Alvarez MI, Ejarque M, Núñez-Roa C, Horrillo D, Maymó-Masip E, Rodríguez MM, Fradera R, de la Rosa JV, Jorba R, Megia A, Zorzano A, Medina-Gómez G, Serena C, Castrillo A, Vendrell J, Fernández-Veledo S. SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity. Nat Immunol 2019; 20(5): 581–592

[99]

Shin KC, Hwang I, Choe SS, Park J, Ji Y, Kim JI, Lee GY, Choi SH, Ching J, Kovalik JP, Kim JB. Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation. Nat Commun 2017; 8(1): 1087

[100]

Caratti G, Stifel U, Caratti B, Jamil AJM, Chung KJ, Kiehntopf M, Gräler MH, Blüher M, Rauch A, Tuckermann JP. Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance. Nat Commun 2023; 14(1): 2271

[101]

Ma J, Hu W, Zhang D, Xie J, Duan C, Liu Y, Wang Y, Xu X, Cheng K, Jin B, Zhang Y, Zhuang R. CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype. J Transl Med 2021; 19(1): 477

[102]

Duan H, Jing L, Xiang J, Ju C, Wu Z, Liu J, Ma X, Chen X, Liu Z, Feng J, Yan X. CD146 associates with Gp130 to control a macrophage pro-inflammatory program that regulates the metabolic response to obesity. Adv Sci (Weinh) 2022; 9(13): e2103719

[103]

Liu PS, Lin YW, Lee B, McCrady-Spitzer SK, Levine JA, Wei LN. Reducing RIP140 expression in macrophage alters ATM infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance. Diabetes 2014; 63(12): 4021–4031

[104]

Qin Y, Jia L, Liu H, Ma W, Ren X, Li H, Liu Y, Li H, Ma S, Liu M, Li P, Yan J, Zhang J, Guo Y, You H, Guo Y, Rahman NA, Wołczyński S, Kretowski A, Li D, Li X, Ren F, Li X. Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance. Nat Commun 2021; 12(1): 6121

[105]

Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24(10): R453–R462

[106]

Rendra E, Riabov V, Mossel DM, Sevastyanova T, Harmsen MC, Kzhyshkowska J. Reactive oxygen species (ROS) in macrophage activation and function in diabetes. Immunobiology 2019; 224(2): 242–253

[107]

Reczek CR, Chandel NS. ROS-dependent signal transduction. Curr Opin Cell Biol 2015; 33: 8–13

[108]

Kang YH, Cho MH, Kim JY, Kwon MS, Peak JJ, Kang SW, Yoon SY, Song Y. Impaired macrophage autophagy induces systemic insulin resistance in obesity. Oncotarget 2016; 7(24): 35577–35591

[109]

Wang C, Chao Y, Xu W, Liu Z, Wang H, Huang K. Myeloid FBW7 deficiency disrupts redox homeostasis and aggravates dietary-induced insulin resistance. Redox Biol 2020; 37: 101688

[110]

Acín-Pérez R, Iborra S, Martí-Mateos Y, Cook ECL, Conde-Garrosa R, Petcherski A, Muñoz MDM, Martínez de Mena R, Krishnan KC, Jiménez C, Bolaños JP, Laakso M, Lusis AJ, Shirihai OS, Sancho D, Enríquez JA. Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity. Nat Metab 2020; 2(9): 974–988

[111]

Ahn YJ, Wang L, Tavakoli S, Nguyen HN, Short JD, Asmis R. Glutaredoxin 1 controls monocyte reprogramming during nutrient stress and protects mice against obesity and atherosclerosis in a sex-specific manner. Nat Commun 2022; 13(1): 790

[112]

Han MS, Jung DY, Morel C, Lakhani SA, Kim JK, Flavell RA, Davis RJ. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 2013; 339(6116): 218–222

[113]

Desai HR, Sivasubramaniyam T, Revelo XS, Schroer SA, Luk CT, Rikkala PR, Metherel AH, Dodington DW, Park YJ, Kim MJ, Rapps JA, Besla R, Robbins CS, Wagner KU, Bazinet RP, Winer DA, Woo M. Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation. Sci Rep 2017; 7(1): 7653

[114]

Kubota T, Inoue M, Kubota N, Takamoto I, Mineyama T, Iwayama K, Tokuyama K, Moroi M, Ueki K, Yamauchi T, Kadowaki T. Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity. Nat Commun 2018; 9(1): 4863

[115]

Saito N, Kimura S, Miyamoto T, Fukushima S, Amagasa M, Shimamoto Y, Nishioka C, Okamoto S, Toda C, Washio K, Asano A, Miyoshi I, Takahashi E, Kitamura H. Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice. Biochem Biophys Rep 2017; 9: 322–329

[116]

Yang Y, Li X, Luan HH, Zhang B, Zhang K, Nam JH, Li Z, Fu M, Munk A, Zhang D, Wang S, Liu Y, Albuquerque JP, Ong Q, Li R, Wang Q, Robert ME, Perry RJ, Chung D, Shulman GI, Yang X. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance. Proc Natl Acad Sci U S A 2020; 117(28): 16616–16625

[117]

Kim GD, Ng HP, Patel N, Mahabeleshwar GH. Kruppel-like factor 6 and miR-223 signaling axis regulates macrophage-mediated inflammation. FASEB J 2019; 33(10): 10902–10915

[118]

Voisin M, Shrestha E, Rollet C, Nikain CA, Josefs T, Mahé M, Barrett TJ, Chang HR, Ruoff R, Schneider JA, Garabedian ML, Zoumadakis C, Yun C, Badwan B, Brown EJ, Mar AC, Schneider RJ, Goldberg IJ, Pineda-Torra I, Fisher EA, Garabedian MJ. Inhibiting LXRα phosphorylation in hematopoietic cells reduces inflammation and attenuates atherosclerosis and obesity in mice. Commun Biol 2021; 4(1): 420

[119]

Ikeda Y, Watanabe H, Shiuchi T, Hamano H, Horinouchi Y, Imanishi M, Goda M, Zamami Y, Takechi K, Izawa-Ishizawa Y, Miyamoto L, Ishizawa K, Aihara KI, Tsuchiya K, Tamaki T. Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice. Diabetologia 2020; 63(8): 1588–1602

[120]

Joffin N, Gliniak CM, Funcke JB, Paschoal VA, Crewe C, Chen S, Gordillo R, Kusminski CM, Oh DY, Geldenhuys WJ, Scherer PE. Adipose tissue macrophages exert systemic metabolic control by manipulating local iron concentrations. Nat Metab 2022; 4(11): 1474–1494

[121]

Shi M, Huang XY, Ren XY, Wei XY, Ma Y, Lin ZZ, Liu DT, Song L, Zhao TJ, Li G, Yao L, Zhu M, Zhang C, Xie C, Wu Y, Wu HM, Fan LP, Ou J, Zhan YH, Lin SY, Lin SC. AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1. Nat Cell Biol 2021; 23(3): 268–277

[122]

Jiang H, Ding X, Cao Y, Wang H, Zeng W. Dense intra-adipose sympathetic arborizations are essential for cold-induced beiging of mouse white adipose tissue. Cell Metab 2017; 26(4): 686–692.e3

[123]

Hsu JW, Nien CY, Yeh SC, Tsai FY, Chen HW, Lee TS, Chen SL, Kao YH, Tsou TC. Phthalate exposure causes browning-like effects on adipocytes in vitro and in vivo. Food Chem Toxicol 2020; 142: 111487

[124]

Picoli CC, Gilio GR, Henriques F, Leal LG, Besson JC, Lopes MA, Franzoi de Moraes SM, Hernandes L, Batista Junior ML, Peres SB. Resistance exercise training induces subcutaneous and visceral adipose tissue browning in Swiss mice. J Appl Physiol 2020; 129(1): 66–74

[125]

Zaror-Behrens G, Himms-Hagen J. Cold-stimulated sympathetic activity in brown adipose tissue of obese (ob/ob) mice. Am J Physiol 1983; 244(4): E361–E366

[126]

Sigurdson SL, Himms-Hagen J. Control of norepinephrine turnover in brown adipose tissue of Syrian hamsters. Am J Physiol 1988; 254(6 Pt 2): R960–R968

[127]

Hücking K, Hamilton-Wessler M, Ellmerer M, Bergman RN. Burst-like control of lipolysis by the sympathetic nervous system in vivo. J Clin Invest 2003; 111(2): 257–264

[128]

Chouchani ET, Kazak L, Spiegelman BM. New advances in adaptive thermogenesis: UCP1 and beyond. Cell Metab 2019; 29(1): 27–37

[129]

Sakamoto T, Takahashi N, Sawaragi Y, Naknukool S, Yu R, Goto T, Kawada T. Inflammation induced by RAW macrophages suppresses UCP1 mRNA induction via ERK activation in 10T1/2 adipocytes. Am J Physiol Cell Physiol 2013; 304(8): C729–C738

[130]

Goto T, Naknukool S, Yoshitake R, Hanafusa Y, Tokiwa S, Li Y, Sakamoto T, Nitta T, Kim M, Takahashi N, Yu R, Daiyasu H, Seno S, Matsuda H, Kawada T. Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes. Cytokine 2016; 77: 107–114

[131]

Zhou H, Wang H, Yu M, Schugar RC, Qian W, Tang F, Liu W, Yang H, McDowell RE, Zhao J, Gao J, Dongre A, Carman JA, Yin M, Drazba JA, Dent R, Hine C, Chen YR, Smith JD, Fox PL, Brown JM, Li X. IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes. Nat Immunol 2020; 21(10): 1219–1231

[132]

Zou W, Rohatgi N, Brestoff JR, Moley JR, Li Y, Williams JW, Alippe Y, Pan H, Pietka TA, Mbalaviele G, Newberry EP, Davidson NO, Dey A, Shoghi KI, Head RD, Wickline SA, Randolph GJ, Abumrad NA, Teitelbaum SL. Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure. J Clin Invest 2020; 130(5): 2644–2656

[133]

Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, Mukundan L, Brombacher F, Locksley RM, Chawla A. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 2011; 480(7375): 104–108

[134]

Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, Palmiter RD, Chawla A. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 2014; 157(6): 1292–1308

[135]

Fischer K, Ruiz HH, Jhun K, Finan B, Oberlin DJ, van der Heide V, Kalinovich AV, Petrovic N, Wolf Y, Clemmensen C, Shin AC, Divanovic S, Brombacher F, Glasmacher E, Keipert S, Jastroch M, Nagler J, Schramm KW, Medrikova D, Collden G, Woods SC, Herzig S, Homann D, Jung S, Nedergaard J, Cannon B, Tschöp MH, Müller TD, Buettner C. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat Med 2017; 23(5): 623–630

[136]

Balter NJ, Schwartz SL. Accumulation of norepinephrine by macrophages and relationships to known uptake processes. J Pharmacol Exp Ther 1977; 201(3): 636–643

[137]

Czimmerer Z, Varga T, Poliska S, Nemet I, Szanto A, Nagy L. Identification of novel markers of alternative activation and potential endogenous PPARγ ligand production mechanisms in human IL-4 stimulated differentiating macrophages. Immunobiology 2012; 217(12): 1301–1314

[138]

Pirzgalska RM, Seixas E, Seidman JS, Link VM, Sánchez NM, Mahú I, Mendes R, Gres V, Kubasova N, Morris I, Arús BA, Larabee CM, Vasques M, Tortosa F, Sousa AL, Anandan S, Tranfield E, Hahn MK, Iannacone M, Spann NJ, Glass CK, Domingos AI. Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nat Med 2017; 23(11): 1309–1318

[139]

Wang YN, Tang Y, He Z, Ma H, Wang L, Liu Y, Yang Q, Pan D, Zhu C, Qian S, Tang QQ. Slit3 secreted from M2-like macrophages increases sympathetic activity and thermogenesis in adipose tissue. Nat Metab 2021; 3(11): 1536–1551

[140]

Knights AJ, Liu S, Ma Y, Nudell VS, Perkey E, Sorensen MJ, Kennedy RT, Maillard I, Ye L, Jun H, Wu J. Acetylcholine-synthesizing macrophages in subcutaneous fat are regulated by β2 -adrenergic signaling. EMBO J 2021; 40(24): e106061

[141]

Jun H, Yu H, Gong J, Jiang J, Qiao X, Perkey E, Kim DI, Emont MP, Zestos AG, Cho JS, Liu J, Kennedy RT, Maillard I, Xu XZS, Wu J. An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling. Nat Med 2018; 24(6): 814–822

[142]

Jun H, Ma Y, Chen Y, Gong J, Liu S, Wang J, Knights AJ, Qiao X, Emont MP, Xu XZS, Kajimura S, Wu J. Adrenergic-independent signaling via CHRNA2 regulates beige fat activation. Dev Cell 2020; 54(1): 106–116.e5

[143]

Schon EA, DiMauro S, Hirano M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat Rev Genet 2012; 13(12): 878–890

[144]

Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 2006; 103(5): 1283–1288

[145]

Gustafsson AB, Dorn GW 2nd. Evolving and expanding the roles of mitophagy as a homeostatic and pathogenic process. Physiol Rev 2019; 99(1): 853–892

[146]

Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol 2020; 21(2): 85–100

[147]

Liu D, Gao Y, Liu J, Huang Y, Yin J, Feng Y, Shi L, Meloni BP, Zhang C, Zheng M, Gao J. Intercellular mitochondrial transfer as a means of tissue revitalization. Signal Transduct Target Ther 2021; 6(1): 65

[148]

Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 2007; 462(2): 245–253

[149]

Pang Y, Zhang C, Gao J. Macrophages as emerging key players in mitochondrial transfers. Front Cell Dev Biol 2021; 9: 747377

[150]

Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, Rowlands DJ, Quadri SK, Bhattacharya S, Bhattacharya J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med 2012; 18(5): 759–765

[151]

Liu CS, Chang JC, Kuo SJ, Liu KH, Lin TT, Cheng WL, Chuang SF. Delivering healthy mitochondria for the therapy of mitochondrial diseases and beyond. Int J Biochem Cell Biol 2014; 53: 141–146

[152]

Hsu YC, Wu YT, Yu TH, Wei YH. Mitochondria in mesenchymal stem cell biology and cell therapy: from cellular differentiation to mitochondrial transfer. Semin Cell Dev Biol 2016; 52: 119–131

[153]

van der Vlist M, Raoof R, Willemen HLDM, Prado J, Versteeg S, Martin Gil C, Vos M, Lokhorst RE, Pasterkamp RJ, Kojima T, Karasuyama H, Khoury-Hanold W, Meyaard L, Eijkelkamp N. Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain. Neuron 2022; 110(4): 613–626.e9

[154]

Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL Jr, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL. Intercellular mitochondria transfer to macrophages regulates white adipose tissue homeostasis and is impaired in obesity. Cell Metab 2021; 33(2): 270–282.e8

[155]

Rosina M, Ceci V, Turchi R, Chuan L, Borcherding N, Sciarretta F, Sánchez-Díaz M, Tortolici F, Karlinsey K, Chiurchiù V, Fuoco C, Giwa R, Field RL, Audano M, Arena S, Palma A, Riccio F, Shamsi F, Renzone G, Verri M, Crescenzi A, Rizza S, Faienza F, Filomeni G, Kooijman S, Rufini S, de Vries AAF, Scaloni A, Mitro N, Tseng YH, Hidalgo A, Zhou B, Brestoff JR, Aquilano K, Lettieri-Barbato D. Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue. Cell Metab 2022; 34(4): 533–548.e12

[156]

Borcherding N, Jia W, Giwa R, Field RL, Moley JR, Kopecky BJ, Chan MM, Yang BQ, Sabio JM, Walker EC, Osorio O, Bredemeyer AL, Pietka T, Alexander-Brett J, Morley SC, Artyomov MN, Abumrad NA, Schilling J, Lavine K, Crewe C, Brestoff JR. Dietary lipids inhibit mitochondria transfer to macrophages to divert adipocyte-derived mitochondria into the blood. Cell Metab 2022; 34(10): 1499–1513.e8

[157]

Marcelin G, Gautier EL, Clément K. Adipose tissue fibrosis in obesity: etiology and challenges. Annu Rev Physiol 2022; 84(1): 135–155

[158]

Sorisky A, Molgat AS, Gagnon A. Macrophage-induced adipose tissue dysfunction and the preadipocyte: should I stay (and differentiate) or should I go?. Adv Nutr 2013; 4(1): 67–75

[159]

Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest 2017; 127(1): 74–82

[160]

Marcelin G, Ferreira A, Liu Y, Atlan M, Aron-Wisnewsky J, Pelloux V, Botbol Y, Ambrosini M, Fradet M, Rouault C, Hénégar C, Hulot JS, Poitou C, Torcivia A, Nail-Barthelemy R, Bichet JC, Gautier EL, Clément K. A PDGFRα-mediated switch toward CD9high adipocyte progenitors controls obesity-induced adipose tissue fibrosis. Cell Metab 2017; 25(3): 673–685

[161]

Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, Louche K, Bourlier V, Roussel B, Gui P, Grober J, Štich V, Rossmeislová L, Zakaroff-Girard A, Bouloumié A, Viguerie N, Moro C, Tavernier G, Langin D. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep 2014; 7(4): 1116–1129

[162]

Tanaka M, Ikeda K, Suganami T, Komiya C, Ochi K, Shirakawa I, Hamaguchi M, Nishimura S, Manabe I, Matsuda T, Kimura K, Inoue H, Inagaki Y, Aoe S, Yamasaki S, Ogawa Y. Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis. Nat Commun 2014; 5(1): 4982

[163]

Memetimin H, Li D, Tan K, Zhou C, Liang Y, Wu Y, Wang S. Myeloid-specific deletion of thrombospondin 1 protects against inflammation and insulin resistance in long-term diet-induced obese male mice. Am J Physiol Endocrinol Metab 2018; 315(6): E1194–E1203

[164]

Rabhi N, Desevin K, Belkina AC, Tilston-Lunel A, Varelas X, Layne MD, Farmer SR. Obesity-induced senescent macrophages activate a fibrotic transcriptional program in adipocyte progenitors. Life Sci Alliance 2022; 5(5): e202101286

[165]

Pellegrinelli V, Rodriguez-Cuenca S, Rouault C, Figueroa-Juarez E, Schilbert H, Virtue S, Moreno-Navarrete JM, Bidault G, Vázquez-Borrego MC, Dias AR, Pucker B, Dale M, Campbell M, Carobbio S, Lin YH, Vacca M, Aron-Wisnewsky J, Mora S, Masiero MM, Emmanouilidou A, Mukhopadhyay S, Dougan G, den Hoed M, Loos RJF, Fernández-Real JM, Chiarugi D, Clément K, Vidal-Puig A. Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance. Nat Metab 2022; 4(4): 476–494

[166]

Madsen DH, Leonard D, Masedunskas A, Moyer A, Jürgensen HJ, Peters DE, Amornphimoltham P, Selvaraj A, Yamada SS, Brenner DA, Burgdorf S, Engelholm LH, Behrendt N, Holmbeck K, Weigert R, Bugge TH. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway. J Cell Biol 2013; 202(6): 951–966

[167]

Müller G. Microvesicles/exosomes as potential novel biomarkers of metabolic diseases. Diabetes Metab Syndr Obes 2012; 5: 247–282

[168]

Mallory AC, Reinhart BJ, Jones-Rhoades MW, Tang G, Zamore PD, Barton MK, Bartel DP. MicroRNA control of PHABULOSA in leaf development: importance of pairing to the microRNA 5′ region. EMBO J 2004; 23(16): 3356–3364

[169]

Ameres SL, Martinez J, Schroeder R. Molecular basis for target RNA recognition and cleavage by human RISC. Cell 2007; 130(1): 101–112

[170]

Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W, Li P, Olefsky JM. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 2017; 171(2): 372–384.e12

[171]

Ying W, Gao H, Dos Reis FCG, Bandyopadhyay G, Ofrecio JM, Luo Z, Ji Y, Jin Z, Ly C, Olefsky JM. MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab 2021; 33(4): 781–790.e5

[172]

Tian F, Tang P, Sun Z, Zhang R, Zhu D, He J, Liao J, Wan Q, Shen J. miR-210 in exosomes derived from macrophages under high glucose promotes mouse diabetic obesity pathogenesis by suppressing NDUFA4 expression. J Diabetes Res 2020; 2020: 6894684

[173]

Li L, Zuo H, Huang X, Shen T, Tang W, Zhang X, An T, Dou L, Li J. Bone marrow macrophage-derived exosomal miR-143-5p contributes to insulin resistance in hepatocytes by repressing MKP5. Cell Prolif 2021; 54(12): e13140

[174]

Qian B, Yang Y, Tang N, Wang J, Sun P, Yang N, Chen F, Wu T, Sun T, Li Y, Chang X, Zhu Y, Zhang Y, Han X. M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice. Diabetologia 2021; 64(9): 2037–2051

[175]

Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 2009; 15(8): 914–920

[176]

Surendar J, Karunakaran I, Frohberger SJ, Koschel M, Hoerauf A, Hübner MP. Macrophages mediate increased CD8 T cell inflammation during weight loss in formerly obese mice. Front Endocrinol (Lausanne) 2020; 11: 257

[177]

Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117(1): 175–184

[178]

Odegaard JI, Chawla A. Alternative macrophage activation and metabolism. Annu Rev Pathol 2011; 6(1): 275–297

[179]

Morris DL, Cho KW, Delproposto JL, Oatmen KE, Geletka LM, Martinez-Santibanez G, Singer K, Lumeng CN. Adipose tissue macrophages function as antigen-presenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes 2013; 62(8): 2762–2772

[180]

Cho KW, Morris DL, DelProposto JL, Geletka L, Zamarron B, Martinez-Santibanez G, Meyer KA, Singer K, O’Rourke RW, Lumeng CN. An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation. Cell Rep 2014; 9(2): 605–617

[181]

Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I, Aron-Wisnewsky J, Lacroix-Desmazes S, Bayry J, Kaveri SV, Clément K, André S, Guerre-Millo M. T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes. Diabetes 2014; 63(6): 1966–1977

[182]

Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46(11): 2347–2355

[183]

Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol (Lausanne) 2016; 7: 30

[184]

Fischer-Posovszky P, Wang QA, Asterholm IW, Rutkowski JM, Scherer PE. Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology 2011; 152(8): 3074–3081

[185]

Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M, Cinti S. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 2008; 49(7): 1562–1568

[186]

Haka AS, Barbosa-Lorenzi VC, Lee HJ, Falcone DJ, Hudis CA, Dannenberg AJ, Maxfield FR. Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation. J Lipid Res 2016; 57(6): 980–992

[187]

Hill AA, Reid Bolus W, Hasty AH. A decade of progress in adipose tissue macrophage biology. Immunol Rev 2014; 262(1): 134–152

[188]

Ruggiero AD, Key CC, Kavanagh K. Adipose tissue macrophage polarization in healthy and unhealthy obesity. Front Nutr 2021; 8: 625331

[189]

Pang C, Gao Z, Yin J, Zhang J, Jia W, Ye J. Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity. Am J Physiol Endocrinol Metab 2008; 295(2): E313–E322

[190]

Xu F, Burk D, Gao Z, Yin J, Zhang X, Weng J, Ye J. Angiogenic deficiency and adipose tissue dysfunction are associated with macrophage malfunction in SIRT1-/- mice. Endocrinology 2012; 153(4): 1706–1716

[191]

Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest 2007; 117(9): 2362–2368

[192]

Fan Y, Ye J, Shen F, Zhu Y, Yeghiazarians Y, Zhu W, Chen Y, Lawton MT, Young WL, Yang GY. Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro. J Cereb Blood Flow Metab 2008; 28(1): 90–98

[193]

Ligresti G, Aplin AC, Zorzi P, Morishita A, Nicosia RF. Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury. Arterioscler Thromb Vasc Biol 2011; 31(5): 1151–1159

[194]

Mathis D. Immunological goings-on in visceral adipose tissue. Cell Metab 2013; 17(6): 851–859

[195]

Cho CH, Koh YJ, Han J, Sung HK, Jong Lee H, Morisada T, Schwendener RA, Brekken RA, Kang G, Oike Y, Choi TS, Suda T, Yoo OJ, Koh GY. Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ Res 2007; 100(4): e47–e57

[196]

Bourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C, Galitzky J, Lafontan M, Karpe F, Frayn KN, Bouloumié A. Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 2008; 117(6): 806–815

[197]

Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 2001; 108(1): 73–81

[198]

Zhao J, Wang L, Dong X, Hu X, Zhou L, Liu Q, Song B, Wu Q, Li L. The c-Jun N-terminal kinase (JNK) pathway is activated in human interstitial cystitis (IC) and rat protamine sulfate induced cystitis. Sci Rep 2016; 6(1): 19670

[199]

Chen YR, Tan TH. The c-Jun N-terminal kinase pathway and apoptotic signaling (review). Int J Oncol 2000; 16(4): 651–662

[200]

Mitchell S, Vargas J, Hoffmann A. Signaling via the NFκB system. Wiley Interdiscip Rev Syst Biol Med 2016; 8(3): 227–241

[201]

Rios R, Silva HBFD, Carneiro NVQ, Pires AO, Carneiro TCB, Costa RDS, Marques CR, Machado MSS, Velozo EDS, Silva TMGD, Silva TMSD, Conceição AS, Alcântara-Neves NM, Figueiredo CA. Solanum paniculatum L. decreases levels of inflammatory cytokines by reducing NFKB, TBET and GATA3 gene expression in vitro. J Ethnopharmacol 2017; 209: 32–40

[202]

Peiró C, Lorenzo Ó, Carraro R, Sánchez-Ferrer CF. IL-1β inhibition in cardiovascular complications associated to diabetes mellitus. Front Pharmacol 2017; 8: 363

[203]

Dinarello CA. A clinical perspective of IL-1β as the gatekeeper of inflammation. Eur J Immunol 2011; 41(5): 1203–1217

[204]

Schultz O, Oberhauser F, Saech J, Rubbert-Roth A, Hahn M, Krone W, Laudes M. Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases. PLoS One 2010; 5(12): e14328

[205]

Taylor PC, Feldmann M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat Rev Rheumatol 2009; 5(10): 578–582

[206]

Wang Q, Li H, Xiao Y, Li S, Li B, Zhao X, Ye L, Guo B, Chen X, Ding Y, Bao C. Locally controlled delivery of TNFα antibody from a novel glucose-sensitive scaffold enhances alveolar bone healing in diabetic conditions. J Control Release 2015; 206: 232–242

[207]

Paquot N, Castillo MJ, Lefèbvre PJ, Scheen AJ. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab 2000; 85(3): 1316–1319

[208]

Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996; 45(7): 881–885

[209]

Li P, Lu M, Nguyen MTA, Bae EJ, Chapman J, Feng D, Hawkins M, Pessin JE, Sears DD, Nguyen AK, Amidi A, Watkins SM, Nguyen U, Olefsky JM. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J Biol Chem 2010; 285(20): 15333–15345

[210]

Li C, Menoret A, Farragher C, Ouyang Z, Bonin C, Holvoet P, Vella AT, Zhou B. Single cell transcriptomics based-MacSpectrum reveals novel macrophage activation signatures in diseases. JCI Insight 2019; 5(10): e126453

[211]

Sárvári AK, Van Hauwaert EL, Markussen LK, Gammelmark E, Marcher AB, Ebbesen MF, Nielsen R, Brewer JR, Madsen JGS, Mandrup S. Plasticity of epididymal adipose tissue in response to diet-induced obesity at single-nucleus resolution. Cell Metab 2021; 33(2): 437–453.e5

[212]

Burl RB, Ramseyer VD, Rondini EA, Pique-Regi R, Lee YH, Granneman JG. Deconstructing adipogenesis induced by β3-adrenergic receptor activation with single-cell expression profiling. Cell Metab 2018; 28(2): 300–309.e4

[213]

Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, Lundgren P, Bleriot C, Liu Z, Deczkowska A, Keren-Shaul H, David E, Zmora N, Eldar SM, Lubezky N, Shibolet O, Hill DA, Lazar MA, Colonna M, Ginhoux F, Shapiro H, Elinav E, Amit I. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent Manner. Cell 2019; 178(3): 686–698.e14

[214]

Hill DA, Lim HW, Kim YH, Ho WY, Foong YH, Nelson VL, Nguyen HCB, Chegireddy K, Kim J, Habertheuer A, Vallabhajosyula P, Kambayashi T, Won KJ, Lazar MA. Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc Natl Acad Sci U S A 2018; 115(22): E5096–E5105

[215]

Sharma M, Schlegel M, Brown EJ, Sansbury BE, Weinstock A, Afonso MS, Corr EM, van Solingen C, Shanley LC, Peled D, Ramasamy R, Schmidt AM, Spite M, Fisher EA, Moore KJ. Netrin-1 alters adipose tissue macrophage fate and function in obesity. Immunometabolism 2019; 1(2): e190010

[216]

Weinstock A, Brown EJ, Garabedian ML, Pena S, Sharma M, Lafaille J, Moore KJ, Fisher EA. Single-cell RNA sequencing of visceral adipose tissue leukocytes reveals that caloric restriction following obesity promotes the accumulation of a distinct macrophage population with features of phagocytic cells. Immunometabolism 2019; 1(1): e190008

[217]

Xu X, Grijalva A, Skowronski A, van Eijk M, Serlie MJ, Ferrante AW Jr. Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab 2013; 18(6): 816–830

[218]

Cottam MA, Caslin HL, Winn NC, Hasty AH. Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice. Nat Commun 2022; 13(1): 2950

[219]

Saberi M, Woods NB, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, Verma IM, Olefsky JM. Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab 2009; 10(5): 419–429

[220]

Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 2005; 11(2): 191–198

[221]

Yu M, Zhou H, Zhao J, Xiao N, Roychowdhury S, Schmitt D, Hu B, Ransohoff RM, Harding CV, Hise AG, Hazen SL, DeFranco AL, Fox PL, Morton RE, Dicorleto PE, Febbraio M, Nagy LE, Smith JD, Wang JA, Li X. MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases. J Exp Med 2014; 211(5): 887–907

[222]

Li X, Ren Y, Chang K, Wu W, Griffiths HR, Lu S, Gao D. Adipose tissue macrophages as potential targets for obesity and metabolic diseases. Front Immunol 2023; 14: 1153915

[223]

Lazarov T, Juarez-Carreño S, Cox N, Geissmann F. Physiology and diseases of tissue-resident macrophages. Nature 2023; 618(7966): 698–707

[224]

Dror E, Dalmas E, Meier DT, Wueest S, Thévenet J, Thienel C, Timper K, Nordmann TM, Traub S, Schulze F, Item F, Vallois D, Pattou F, Kerr-Conte J, Lavallard V, Berney T, Thorens B, Konrad D, Böni-Schnetzler M, Donath MY. Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol 2017; 18(3): 283–292

[225]

Takikawa A, Mahmood A, Nawaz A, Kado T, Okabe K, Yamamoto S, Aminuddin A, Senda S, Tsuneyama K, Ikutani M, Watanabe Y, Igarashi Y, Nagai Y, Takatsu K, Koizumi K, Imura J, Goda N, Sasahara M, Matsumoto M, Saeki K, Nakagawa T, Fujisaka S, Usui I, Tobe K. HIF-1α in myeloid cells promotes adipose tissue remodeling toward insulin resistance. Diabetes 2016; 65(12): 3649–3659

[226]

Branco-Price C, Zhang N, Schnelle M, Evans C, Katschinski DM, Liao D, Ellies L, Johnson RS. Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success. Cancer Cell 2012; 21(1): 52–65

[227]

NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017; 390(10113): 2627–2642

[228]

Maffeis C, Olivieri F, Valerio G, Verduci E, Licenziati MR, Calcaterra V, Pelizzo G, Salerno M, Staiano A, Bernasconi S, Buganza R, Crinò A, Corciulo N, Corica D, Destro F, Di Bonito P, Di Pietro M, Di Sessa A, deSanctis L, Faienza MF, Filannino G, Fintini D, Fornari E, Franceschi R, Franco F, Franzese A, Giusti LF, Grugni G, Iafusco D, Iughetti L, Lera R, Limauro R, Maguolo A, Mancioppi V, Manco M, Del Giudice EM, Morandi A, Moro B, Mozzillo E, Rabbone I, Peverelli P, Predieri B, Purromuto S, Stagi S, Street ME, Tanas R, Tornese G, Umano GR, Wasniewska M. The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery. Ital J Pediatr 2023; 49(1): 69

[229]

Wharton S, Lau DCW, Vallis M, Sharma AM, Biertho L, Campbell-Scherer D, Adamo K, Alberga A, Bell R, Boulé N, Boyling E, Brown J, Calam B, Clarke C, Crowshoe L, Divalentino D, Forhan M, Freedhoff Y, Gagner M, Glazer S, Grand C, Green M, Hahn M, Hawa R, Henderson R, Hong D, Hung P, Janssen I, Jacklin K, Johnson-Stoklossa C, Kemp A, Kirk S, Kuk J, Langlois MF, Lear S, McInnes A, Macklin D, Naji L, Manjoo P, Morin MP, Nerenberg K, Patton I, Pedersen S, Pereira L, Piccinini-Vallis H, Poddar M, Poirier P, Prud’homme D, Salas XR, Rueda-Clausen C, Russell-Mayhew S, Shiau J, Sherifali D, Sievenpiper J, Sockalingam S, Taylor V, Toth E, Twells L, Tytus R, Walji S, Walker L, Wicklum S. Obesity in adults: a clinical practice guideline. CMAJ 2020; 192(31): E875–E891

[230]

Wen X, Zhang B, Wu B, Xiao H, Li Z, Li R, Xu X, Li T. Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal Transduct Target Ther 2022; 7(1): 298

[231]

Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 2012; 122(6): 253–270

[232]

Song R. Mechanism of metformin: a tale of two sites. Diabetes Care 2016; 39(2): 187–189

[233]

Feng X, Chen W, Ni X, Little PJ, Xu S, Tang L, Weng J. Metformin, macrophage dysfunction and atherosclerosis. Front Immunol 2021; 12: 682853

[234]

Jing Y, Wu F, Li D, Yang L, Li Q, Li R. Metformin improves obesity-associated inflammation by altering macrophages polarization. Mol Cell Endocrinol 2018; 461: 256–264

[235]

Ma T, Tian X, Zhang B, Li M, Wang Y, Yang C, Wu J, Wei X, Qu Q, Yu Y, Long S, Feng JW, Li C, Zhang C, Xie C, Wu Y, Xu Z, Chen J, Yu Y, Huang X, He Y, Yao L, Zhang L, Zhu M, Wang W, Wang ZC, Zhang M, Bao Y, Jia W, Lin SY, Ye Z, Piao HL, Deng X, Zhang CS, Lin SC. Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature 2022; 603(7899): 159–165

[236]

Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017; 60(9): 1577–1585

[237]

Zhuge F, Ni Y, Nagashimada M, Nagata N, Xu L, Mukaida N, Kaneko S, Ota T. DPP-4 inhibition by linagliptin attenuates obesity-related inflammation and insulin resistance by regulating M1/M2 macrophage polarization. Diabetes 2016; 65(10): 2966–2979

[238]

Zheng W, Zhou J, Song S, Kong W, Xia W, Chen L, Zeng T. Dipeptidyl-peptidase 4 inhibitor sitagliptin ameliorates hepatic insulin resistance by modulating inflammation and autophagy in ob/ob mice. Int J Endocrinol 2018; 2018: 8309723

[239]

Xu L, Nagata N, Nagashimada M, Zhuge F, Ni Y, Chen G, Mayoux E, Kaneko S, Ota T. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine 2017; 20: 137–149

[240]

Xu L, Nagata N, Chen G, Nagashimada M, Zhuge F, Ni Y, Sakai Y, Kaneko S, Ota T. Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet. BMJ Open Diabetes Res Care 2019; 7(1): e000783

[241]

Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017; 17(1): 20–37

[242]

Hong EJ, Choi DG, Shim MS. Targeted and effective photodynamic therapy for cancer using functionalized nanomaterials. Acta Pharm Sin B 2016; 6(4): 297–307

[243]

Kang L, Gao Z, Huang W, Jin M, Wang Q. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment. Acta Pharm Sin B 2015; 5(3): 169–175

[244]

Ngo W, Ahmed S, Blackadar C, Bussin B, Ji Q, Mladjenovic SM, Sepahi Z, Chan WCW. Why nanoparticles prefer liver macrophage cell uptake in vivo. Adv Drug Deliv Rev 2022; 185: 114238

[245]

Thakor AS, Jokerst JV, Ghanouni P, Campbell JL, Mittra E, Gambhir SS. Clinically approved nanoparticle imaging agents. J Nucl Med 2016; 57(12): 1833–1837

[246]

Vijayan V, Uthaman S, Park IK. Cell membrane coated nanoparticles: an emerging biomimetic nanoplatform for targeted bioimaging and therapy. Adv Exp Med Biol 2018; 1064: 45–59

[247]

Khatoon N, Zhang Z, Zhou C, Chu M. Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery. Biomater Sci 2022; 10(5): 1193–1208

[248]

Hou KK, Pan H, Lanza GM, Wickline SA. Melittin derived peptides for nanoparticle based siRNA transfection. Biomaterials 2013; 34(12): 3110–3119

[249]

Zhou HF, Yan H, Pan H, Hou KK, Akk A, Springer LE, Hu Y, Allen JS, Wickline SA, Pham CT. Peptide-siRNA nanocomplexes targeting NF-κB subunit p65 suppress nascent experimental arthritis. J Clin Invest 2014; 124(10): 4363–4374

[250]

Yan H, Duan X, Pan H, Holguin N, Rai MF, Akk A, Springer LE, Wickline SA, Sandell LJ, Pham CT. Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc Natl Acad Sci U S A 2016; 113(41): E6199–E6208

[251]

Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW 2nd, DeFuria J, Jick Z, Greenberg AS, Obin MS. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 2007; 56(12): 2910–2918

[252]

Shimaoka T, Kume N, Minami M, Hayashida K, Kataoka H, Kita T, Yonehara S. Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. J Biol Chem 2000; 275(52): 40663–40666

[253]

He C, Hu Y, Yin L, Tang C, Yin C. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 2010; 31(13): 3657–3666

[254]

Pustylnikov S, Sagar D, Jain P, Khan ZK. Targeting the C-type lectins-mediated host-pathogen interactions with dextran. J Pharm Pharm Sci 2014; 17(3): 371–392

[255]

Ma L, Liu TW, Wallig MA, Dobrucki IT, Dobrucki LW, Nelson ER, Swanson KS, Smith AM. Efficient targeting of adipose tissue macrophages in obesity with polysaccharide nanocarriers. ACS Nano 2016; 10(7): 6952–6962

[256]

Peterson KR, Cottam MA, Kennedy AJ, Hasty AH. Macrophage-targeted therapeutics for metabolic disease. Trends Pharmacol Sci 2018; 39(6): 536–546

[257]

Koning GA, Storm G. Targeted drug delivery systems for the intracellular delivery of macromolecular drugs. Drug Discov Today 2003; 8(11): 482–483

[258]

Metselaar JM, Storm G. Liposomes in the treatment of inflammatory disorders. Expert Opin Drug Deliv 2005; 2(3): 465–476

[259]

Ding BS, Dziubla T, Shuvaev VV, Muro S, Muzykantov VR. Advanced drug delivery systems that target the vascular endothelium. Mol Interv 2006; 6(2): 98–112

[260]

Hua S, Wu SY. The use of lipid-based nanocarriers for targeted pain therapies. Front Pharmacol 2013; 4: 143

[261]

Jain NK, Mishra V, Mehra NK. Targeted drug delivery to macrophages. Expert Opin Drug Deliv 2013; 10(3): 353–367

[262]

Adair JR, Howard PW, Hartley JA, Williams DG, Chester KA. Antibody-drug conjugates — a perfect synergy. Expert Opin Biol Ther 2012; 12(9): 1191–1206

[263]

Harper J, Mao S, Strout P, Kamal A. Selecting an optimal antibody for antibody-drug conjugate therapy: internalization and intracellular localization. Methods Mol Biol 2013; 1045: 41–49

[264]

Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK. Identification of the haemoglobin scavenger receptor. Nature 2001; 409(6817): 198–201

[265]

Etzerodt A, Maniecki MB, Graversen JH, Møller HJ, Torchilin VP, Moestrup SK. Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163. J Control Release 2012; 160(1): 72–80

[266]

Chono S, Tauchi Y, Deguchi Y, Morimoto K. Efficient drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by dexamethasone incorporated into liposomes in atherogenic mice. J Drug Target 2005; 13(4): 267–276

[267]

Gibbons AM, McElvaney NG, Taggart CC, Cryan SA. Delivery of rSLPI in a liposomal carrier for inhalation provides protection against cathepsin L degradation. J Microencapsul 2009; 26(6): 513–522

[268]

Ponzoni M, Pastorino F, Di Paolo D, Perri P, Brignole C. Targeting macrophages as a potential therapeutic intervention: impact on inflammatory diseases and cancer. Int J Mol Sci 2018; 19(7): 1953

[269]

Ghinoi V, Brandi ML. Clodronate: mechanisms of action on bone remodelling and clinical use in osteometabolic disorders. Expert Opin Pharmacother 2002; 3(11): 1643–1656

[270]

van Rooijen N, van Kesteren-Hendrikx E. Clodronate liposomes: perspectives in research and therapeutics. J Liposome Res 2002; 12(1–2): 81–94

[271]

Van Rooijen N, Sanders A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 1994; 174(1–2): 83–93

[272]

Bu L, Gao M, Qu S, Liu D. Intraperitoneal injection of clodronate liposomes eliminates visceral adipose macrophages and blocks high-fat diet-induced weight gain and development of insulin resistance. AAPS J 2013; 15(4): 1001–1011

[273]

Curat CA, Miranville A, Sengenès C, Diehl M, Tonus C, Busse R, Bouloumié A. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 2004; 53(5): 1285–1292

[274]

Takahashi K, Mizuarai S, Araki H, Mashiko S, Ishihara A, Kanatani A, Itadani H, Kotani H. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem 2003; 278(47): 46654–46660

[275]

Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A 2003; 100(12): 7265–7270

[276]

Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes (Lond) 2005; 29(1): 146–150

[277]

Dahlman I, Kaaman M, Olsson T, Tan GD, Bickerton AS, Wåhlén K, Andersson J, Nordström EA, Blomqvist L, Sjögren A, Forsgren M, Attersand A, Arner P. A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects. J Clin Endocrinol Metab 2005; 90(10): 5834–5840

[278]

Di Gregorio GB, Yao-Borengasser A, Rasouli N, Varma V, Lu T, Miles LM, Ranganathan G, Peterson CA, McGehee RE, Kern PA. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes 2005; 54(8): 2305–2313

[279]

Chen A, Mumick S, Zhang C, Lamb J, Dai H, Weingarth D, Mudgett J, Chen H, MacNeil DJ, Reitman ML, Qian S. Diet induction of monocyte chemoattractant protein-1 and its impact on obesity. Obes Res 2005; 13(8): 1311–1320

[280]

Brown GD, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature 2001; 413(6851): 36–37

[281]

Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L, Wong SY, Gordon S. Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med 2002; 196(3): 407–412

[282]

Aouadi M, Tesz GJ, Nicoloro SM, Wang M, Chouinard M, Soto E, Ostroff GR, Czech MP. Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature 2009; 458(7242): 1180–1184

[283]

Soto ER, O’Connell O, Dikengil F, Peters PJ, Clapham PR, Ostroff GR. Targeted delivery of glucan particle encapsulated gallium nanoparticles inhibits HIV growth in human macrophages. J Drug Deliv 2016; 2016: 8520629

[284]

Upadhyay TK, Fatima N, Sharma D, Saravanakumar V, Sharma R. Preparation and characterization of beta-glucan particles containing a payload of nanoembedded rifabutin for enhanced targeted delivery to macrophages. EXCLI J 2017; 16: 210–228

[285]

Mishra V, Gupta U, Jain NK. Influence of different generations of poly(propylene imine) dendrimers on human erythrocytes. Pharmazie 2010; 65(12): 891–895

[286]

Kumar PV, Asthana A, Dutta T, Jain NK. Intracellular macrophage uptake of rifampicin loaded mannosylated dendrimers. J Drug Target 2006; 14(8): 546–556

[287]

Yong SB, Song Y, Kim YH. Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes. Biomaterials 2017; 148: 81–89

[288]

Caballero B. Humans against obesity: who will win?. Adv Nutr 2019; 10(suppl_1): S4–S9

[289]

Green M, Arora K, Prakash S. Microbial medicine: prebiotic and probiotic functional foods to target obesity and metabolic syndrome. Int J Mol Sci 2020; 21(8): 2890

[290]

Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 2013; 17(6): 819–837

[291]

Drucker DJ, Habener JF, Holst JJ. Discovery, characterization, and clinical development of the glucagon-like peptides. J Clin Invest 2017; 127(12): 4217–4227

[292]

Hachiya R, Tanaka M, Itoh M, Suganami T. Molecular mechanism of crosstalk between immune and metabolic systems in metabolic syndrome. Inflamm Regen 2022; 42(1): 13

[293]

Das A, Sinha M, Datta S, Abas M, Chaffee S, Sen CK, Roy S. Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol 2015; 185(10): 2596–2606

[294]

Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol 2013; 120: 163–184

[295]

Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, Schoenfelt KQ, Kuzma JN, Larson I, Billing PS, Landerholm RW, Crouthamel M, Gozal D, Hwang S, Singh PK, Becker L. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab 2014; 20(4): 614–625

[296]

Coats BR, Schoenfelt KQ, Barbosa-Lorenzi VC, Peris E, Cui C, Hoffman A, Zhou G, Fernandez S, Zhai L, Hall BA, Haka AS, Shah AM, Reardon CA, Brady MJ, Rhodes CJ, Maxfield FR, Becker L. Metabolically activated adipose tissue macrophages perform detrimental and beneficial functions during diet-induced obesity. Cell Rep 2017; 20(13): 3149–3161

[297]

Vijay J, Gauthier MF, Biswell RL, Louiselle DA, Johnston JJ, Cheung WA, Belden B, Pramatarova A, Biertho L, Gibson M, Simon MM, Djambazian H, Staffa A, Bourque G, Laitinen A, Nystedt J, Vohl MC, Fraser JD, Pastinen T, Tchernof A, Grundberg E. Single-cell analysis of human adipose tissue identifies depot and disease specific cell types. Nat Metab 2020; 2(1): 97–109

[298]

Boutens L, Hooiveld GJ, Dhingra S, Cramer RA, Netea MG, Stienstra R. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia 2018; 61(4): 942–953

RIGHTS & PERMISSIONS

Higher Education Press

AI Summary AI Mindmap
PDF (3232KB)

2761

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/