Association of mitochondrial dysfunction and lipid metabolism with type 2 diabetes mellitus: A review of literature

Abstract

BACKGROUND: Diabetes mellitus (DM) is one of the most prevalent chronic diseases, and its prevalence continues to increase globally. The impact of mitochondrial dysfunction and lipid metabolism on diabetes mellitus and insulin resistance (IR) has been implicated in several previous reports; however, the results of studies are confusing despite four decades of study.

METHODS/RESULTS: This review has evaluated updated understanding of the role of mitochondrial dysfunction and lipid metabolism on type 2 diabetes, and found that mitochondrial dysfunction and lipid metabolism disorder induce the dysregulation of liver and pancreatic beta cells, insulin resistance, and type 2 diabetes.

CONCLUSION: Mitochondrial dysfunction and lipid metabolism induce metabolic dysregulation and finally increasing the possibility of diabetes.

Key words： Insulin resistance; Type 2 diabetes; Mitochondrial dysfunction; Lipid metabolism

References

1 Aguirre-Rueda D, Guerra-Ojeda S, Aldasoro M, Iradi A, Obrador E, Ortega A, Mauricio M D, Vila J M, Valles S L (2015). Astrocytes protect neurons from Aβ1-42 peptide-induced neurotoxicity increasing TFAM and PGC-1 and decreasing PPAR-g and SIRT-1. Int J Med Sci, 12(1): 48–56

PMID

2 Antos-Krzeminska N, Jarmuszkiewicz W (2014). External NAD(P)H dehydrogenases in Acanthamoeba castellanii mitochondria. Protist, 165(5): 580–593

PMID

3 Bakar M H A, Sarmidi M R, Kai C K, Huri H Z, Yaakob H (2014). Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kB pathways. Int J Mol Sci, 15(12): 22227–22257

PMID

4 Bakhtiyari S, Meshkani R, Taghikhani M, Larijani B, Adeli K (2010). Protein tyrosine phosphatase-1B (PTP-1B) knockdown improves palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Lipids, 45(3): 237–244

PMID

5 Bandyopadhyay G K, Lu M, Avolio E, Siddiqui J A, Gayen J R, Wollam J, Vu C U, Chi N W, O’Connor D T, Mahata S K (2015). Pancreastatin-dependent inflammatory signaling mediates obesity-induced insulin resistance. Diabetes, 64(1): 104–116

PMID

6 Bettaieb A, Matsuo K, Matsuo I, Wang S, Melhem R, Koromilas A E, Haj F G (2012). Protein tyrosine phosphatase 1B deficiency potentiates PERK/eIF2α signaling in brown adipocytes. PLoS One, 7(4): e34412

PMID

7 Bose S K, Kim H, Meyer K, Wolins N, Davidson N O, Ray R (2014). Forkhead box transcription factor regulation and lipid accumulation by hepatitis C virus. J Virol, 88(8): 4195–4203

PMID

8 Camões F, Islinger M, Guimarães S C, Kilaru S, Schuster M, Godinho L F, Steinberg G, Schrader M (2015). New insights into the peroxisomal protein inventory: Acyl-CoA oxidases and-dehydrogenases are an ancient feature of peroxisomes. Biochim Biophys Acta, 1853(1): 111–125

PMID

9 Carey A L, Vorlander C, Reddy-Luthmoodoo M, Natoli A K, Formosa M F, Bertovic D A, Anderson M J, Duffy S J, Kingwell B A (2014). Reduced UCP-1 content in in vitro differentiated beige/brite adipocytes derived from preadipocytes of human subcutaneous white adipose tissues in obesity. PLoS One, 9(3): e91997

PMID

10 Carey B W, Finley L W, Cross J R, Allis C D, Thompson C B (2015). Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature, 518(7539): 413–416

PMID

11 Chen L, Liu T, Zhang S, Zhou J, Wang Y, Di W (2014). Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1α pathway in human ovarian cancer in vitro. J Ovarian Res, 7(1): 115

PMID

12 Chinnery P (2014). Mitochondrial disorders overview. Synonyms: mitochondrial encephalomyopathies, mitochondrial myopathies, oxidative phosphorylation disorders, respiratory chain disorders. GeneReviews Seattle: University of Washington

13 Chinnery P F, Elliott H R, Hudson G, Samuels D C, Relton C L (2012). Epigenetics, epidemiology and mitochondrial DNA diseases. Int J Epidemiol, 41(1): 177–187

PMID

14 Cook J R, Matsumoto M, Banks A S, Kitamura T, Tsuchiya K, Accili D (2015). A Mutant Allele Encoding DNA-Binding-Deficient Foxo1 Differentially Regulates Hepatic Glucose and Lipid Metabolism. Diabetes, 64(6): 1951–1965

15 Czibik G, Steeples V, Yavari A, Ashrafian H (2014). Citric acid cycle intermediates in cardioprotection. Circ Cardiovasc Genet, 7(5): 711–719

15 Dadke S S, Li H C, Kusari A B, Begum N, Kusari J (2000). Elevated expression and activity of protein-tyrosine phosphatase 1B in skeletal muscle of insulin-resistant type II diabetic Goto-Kakizaki rats. Biochem Biophys Res Commun, 274(3): 583–589

PMID

16 de Luca C, Olefsky J M (2008). Inflammation and insulin resistance. FEBS Lett, 582(1): 97–105

PMID

17 Delibegovic M, Bence K K, Mody N, Hong E G, Ko H J, Kim J K, Kahn B B, Neel B G (2007). Improved glucose homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B. Mol Cell Biol, 27(21): 7727–7734

PMID

18 Demine S, Reddy N, Renard P, Raes M, Arnould T (2014). Unraveling biochemical pathways affected by mitochondrial dysfunctions using metabolomic approaches. Metabolites, 4(3): 831–878

PMID

19 Desai G S, Mathews S T (2014). Saliva as a non-invasive diagnostic tool for inflammation and insulin-resistance. World J Diabetes, 5(6): 730–738

PMID

20 Ding H, Zhang Y, Xu C, Hou D, Li J, Zhang Y, Peng W, Zen K, Zhang C Y, Jiang X (2014). Norathyriol reverses obesity- and high-fat-diet-induced insulin resistance in mice through inhibition of PTP1B. Diabetologia, 57(10): 2145–2154

PMID

21 Dudley K J, Sloboda D M, Connor K L, Beltrand J, Vickers M H (2011). Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation. PLoS One, 6(7): e21662

PMID

22 Egger G, Liang G, Aparicio A, Jones P A (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429(6990): 457–463

PMID

23 Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy A L, Normandin D, Cheng A, Himms-Hagen J, Chan C C, Ramachandran C, Gresser M J, Tremblay M L, Kennedy B P (1999). Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science, 283(5407): 1544–1548

PMID

24 Fatland B L, Ke J, Anderson M D, Mentzen W I, Cui L W, Allred C C, Johnston J L, Nikolau B J, Wurtele E S (2002). Molecular characterization of a heteromeric ATP-citrate lyase that generates cytosolic acetyl-coenzyme A in Arabidopsis. Plant Physiol, 130(2): 740–756

PMID

25 Ferber E C, Peck B, Delpuech O, Bell G P, East P, Schulze A (2012). FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ, 19(6): 968–979

PMID

26 Ferla M P, Thrash J C, Giovannoni S J, Patrick W M (2013). New rRNA gene-based phylogenies of the Alphaproteobacteria provide perspective on major groups, mitochondrial ancestry and phylogenetic instability. PLoS One, 8(12): e83383

PMID

27 Forkink M, Manjeri G R, Liemburg-Apers D C, Nibbeling E, Blanchard M, Wojtala A, Smeitink J A, Wieckowski M R, Willems P H, Koopman W J (2014). Mitochondrial hyperpolarization during chronic complex I inhibition is sustained by low activity of complex II, III, IV and V. Biochim Biophys Acta, 1837(8): 1247–1256

PMID

28 Freund-Michel V, Khoyrattee N, Savineau J P, Muller B, Guibert C (2014). Mitochondria: roles in pulmonary hypertension. Int J Biochem Cell Biol, 55: 93–97

PMID

29 Freund-Michel V, Khoyrattee N, Savineau J P, Muller B, Guibert C (2014). Mitochondria: roles in pulmonary hypertension. Int J Biochem Cell Biol, 55: 93–97

PMID

30 Frohman M A (2015). Role of mitochondrial lipids in guiding fission and fusion. J Mol Med (Berl), 93(3): 263–269

PMID

31 Fukao T, Mitchell G, Sass J O, Hori T, Orii K, Aoyama Y (2014). Ketone body metabolism and its defects. J Inherit Metab Dis, 37(4): 541–551

PMID

32 Garcia de la Garma J, Fernandez-Garcia N, Bardisi E, Pallol B, Asensio-Rubio J S, Bru R, Olmos E (2015). New insights into plant salt acclimation: the roles of vesicle trafficking and reactive oxygen species signalling in mitochondria and the endomembrane system. New Phytol, 205(1): 216–239

PMID

33 Ge Z J, Luo S M, Lin F, Liang Q X, Huang L, Wei Y C, Hou Y, Han Z M, Schatten H, Sun Q Y (2014). DNA methylation in oocytes and liver of female mice and their offspring: effects of high-fat-diet-induced obesity. Environ Health Perspect, 122(2): 159–164

PMID

34 Genova M L, Lenaz G (2014). Functional role of mitochondrial respiratory supercomplexes. Biochim Biophys Acta, 1837(4): 427–443

PMID

35 Gogga P, Karbowska J, Meissner W, Kochan Z (2011). Role of leptin in the regulation of lipid and carbohydrate metabolism. Postepy Hig Med Dosw (Online), 65: 255–62

36 Gogoi B, Chatterjee P, Mukherjee S, Buragohain A K, Bhattacharya S, Dasgupta S (2014). A polyphenol rescues lipid induced insulin resistance in skeletal muscle cells and adipocytes. Biochem Biophys Res Commun, 452(3): 382–388

PMID

37 Goldstein B J (1993). Regulation of insulin receptor signaling by protein-tyrosine dephosphorylation. Receptor, 3(1): 1–15

PMID

38 Graham E J, Adler F R (2014). Long-term models of oxidative stress and mitochondrial damage in insulin resistance progression. J Theor Biol, 340: 238–250

PMID

39 Gu P, Liu W, Shao J, Lu B, Wang Y, Jiang W, Jiang S (2010). Protein tyrosine phosphatase 1B gene polymorphisms and obesity-related hypertension: a case-control study in Chinese population. Shengwu Yixue Gongcheng Yu Linchuang, 14(5): 442–446

40 Haj F G, Zabolotny J M, Kim Y B, Kahn B B, Neel B G (2005). Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B-/-mice. J Biol Chem, 280(15): 15038–15046

PMID

41 Harijith A, Ebenezer D L, Natarajan V (2014). Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol, 5: 352

PMID

42 Hasan N M, Longacre M J, Stoker S W, Kendrick M A, MacDonald M J (2015). Mitochondrial malic enzyme 3 is important for insulin secretion in pancreatic β-cells. Mol Endocrinol, 29(3): 396–410

PMID

43 Hiltunen J K, Autio K J, Schonauer M S, Kursu V A, Dieckmann C L, Kastaniotis A J (2010). Mitochondrial fatty acid synthesis and respiration. Biochim Biophys Acta, 1797(6-7): 1195–1202

PMID

44 Hynes M J, Murray S L (2010). ATP-citrate lyase is required for production of cytosolic acetyl coenzyme A and development in Aspergillus nidulans. Eukaryot Cell, 9(7): 1039–1048

PMID

45 Ishii M, Maeda A, Tani S, Akagawa M (2015). Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules. Arch Biochem Biophys, 566: 26–35

PMID

46 Ishii M, Maeda A, Tani S, Akagawa M (2015). Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules. Arch Biochem Biophys, 566: 26–35

PMID

47 Jacobsen S C, Brøns C, Bork-Jensen J, Ribel-Madsen R, Yang B, Lara E, Hall E, Calvanese V, Nilsson E, Jørgensen S W, Mandrup S, Ling C, Fernandez A F, Fraga M F, Poulsen P, Vaag A (2012). Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men. Diabetologia, 55(12): 3341–3349

PMID

48 James A M, Murphy M P (2002). How mitochondrial damage affects cell function. J Biomed Sci, 9(6 Pt 1): 475–487

PMID

49 Javor E D, Cochran E K, Musso C, Young J R, Depaoli A M, Gorden P (2005). Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes, 54(7): 1994–2002

PMID

50 Johnson T O, Ermolieff J, Jirousek M R (2002). Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat Rev Drug Discov, 1(9): 696–709

PMID

51 Ka S O, Song M Y, Bae E J, Park B H (2015). Myeloid SIRT1 regulates macrophage infiltration and insulin sensitivity in mice fed a high-fat diet. J Endocrinol, 224(2): 109–118

PMID

52 Kadota Y, Kazama S, Bajotto G, Kitaura Y, Shimomura Y (2012). Clofibrate-induced reduction of plasma branched-chain amino acid concentrations impairs glucose tolerance in rats. JPEN J Parenter Enteral Nutr, 36(3): 337–343

PMID

53 Kang L, Dai C, Lustig M E, Bonner J S, Mayes W H, Mokshagundam S, James F D, Thompson C S, Lin C T, Perry C G, Anderson E J, Neufer P D, Wasserman D H, Powers A C (2014). Heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion, but not insulin action, in high-fat-fed mice. Diabetes, 63(11): 3699–3710

PMID

54 Kathirvel E, Morgan K, French S W, Morgan T R (2013). Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. Nutr Res, 33(11): 932–941

PMID

55 Kathirvel E, Morgan K, French S W, Morgan T R (2013). Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. Nutr Res, 33(11): 932–941

PMID

56 Khalyfa A, Carreras A, Hakim F, Cunningham J M, Wang Y, Gozal D (2013). Effects of late gestational high-fat diet on body weight, metabolic regulation and adipokine expression in offspring. Int J Obes (Lond), 37(11): 1481–1489

PMID

57 Kim J A, Wei Y, Sowers J R (2008). Role of mitochondrial dysfunction in insulin resistance. Circ Res, 102(4): 401–414

PMID

58 Klaman L D, Boss O, Peroni O D, Kim J K, Martino J L, Zabolotny J M, Moghal N, Lubkin M, Kim Y B, Sharpe A H, Stricker-Krongrad A, Shulman G I, Neel B G, Kahn B B (2000). Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol, 20(15): 5479–5489

PMID

59 Koob S, Reichert A S (2014). Novel intracellular functions of apolipoproteins: the ApoO protein family as constituents of the Mitofilin/MINOS complex determines cristae morphology in mitochondria. Biol Chem, 395(3): 285–296

PMID

60 Kowalski G M, Kloehn J, Burch M L, Selathurai A, Hamley S, Bayol S A, Lamon S, Watt M J, Lee-Young R S, McConville M J, Bruce C R (2015). Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet. Biochim Biophys Acta, 1851(2): 210–219

PMID

61 Krivoruchko A, Zhang Y, Siewers V, Chen Y, Nielsen J (2015). Microbial acetyl-CoA metabolism and metabolic engineering. Metab Eng, 28: 28–42

PMID

62 Kühn K, Yin G, Duncan O, Law S R, Kubiszewski-Jakubiak S, Kaur P, Meyer E, Wang Y, Small C C, Giraud E, Narsai R, Whelan J (2015). Decreasing electron flux through the cytochrome and/or alternative respiratory pathways triggers common and distinct cellular responses dependent on growth conditions. Plant Physiol, 167(1): 228–250

PMID

63 Laafi J, Homedan C, Jacques C, Gueguen N, Schmitt C, Puy H, Reynier P, Carmen Martinez M, Malthièry Y (2014). Pro-oxidant effect of ALA is implicated in mitochondrial dysfunction of HepG2 cells. Biochimie, 106: 157–166

PMID

64 Lees E K, Krol E, Shearer K, Mody N, Gettys T W, Delibegovic M (2015). Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice. Metabolism, 64(2): 305–314

PMID

65 Lian J, Si T, Nair N U, Zhao H (2014). Design and construction of acetyl-CoA overproducing Saccharomyces cerevisiae strains. Metab Eng, 24: 139–149

PMID

66 Lian K, Du C, Liu Y, Zhu D, Yan W, Zhang H, Hong Z, Liu P, Zhang L, Pei H, Zhang J, Gao C, Xin C, Cheng H, Xiong L, Tao L (2015). Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice. Diabetes, 64(1): 49–59

PMID

67 Liu J, Li J, Li W J, Wang C M (2013). The role of uncoupling proteins in diabetes mellitus. J Diabetes Res, 2013: 585897

PMID

68 Liu W, Cao H, Ye C, Chang C, Lu M, Jing Y, Zhang D, Yao X, Duan Z, Xia H, Wang Y C, Jiang J, Liu M F, Yan J, Ying H (2014). Hepatic miR-378 targets p110α and controls glucose and lipid homeostasis by modulating hepatic insulin signalling. Nat Commun, 5(1): 5684

PMID

69 Lynch C J, Adams S H (2014). Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol, 10(12): 723–736

PMID

70 Maassen J A, Janssen G M, ’t Hart L M (2005). Molecular mechanisms of mitochondrial diabetes (MIDD). Ann Med, 37(3): 213–221

PMID

71 Martins A R, Nachbar R T, Gorjao R, Vinolo M A, Festuccia W T, Lambertucci R H, Cury-Boaventura M F, Silveira L R, Curi R, Hirabara S M (2012). Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis, 11(1): 30

PMID

72 McArdle M A, Finucane O M, Connaughton R M, McMorrow A M, Roche H M (2013). Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies. Front Endocrinol (Lausanne), 4: 52

PMID

73 Meshkani R, Taghikhani M, Al-Kateb H, Larijani B, Khatami S, Sidiropoulos G K, Hegele R A, Adeli K (2007). Polymorphisms within the protein tyrosine phosphatase 1B (PTPN1) gene promoter: functional characterization and association with type 2 diabetes and related metabolic traits. Clin Chem, 53(9): 1585–1592

PMID

74 Meshkani R, Taghikhani M, Mosapour A, Larijani B, Khatami S, Khoshbin E, Ahmadvand D, Saeidi P, Maleki A, Yavari K, Nasoohi N, Adeli K (2007). 1484insG polymorphism of the PTPN1 gene is associated with insulin resistance in an Iranian population. Arch Med Res, 38(5): 556–562

PMID

75 Mizukami H, Takahashi K, Inaba W, Tsuboi K, Osonoi S, Yoshida T, Yagihashi S (2014). Involvement of oxidative stress-induced DNA damage, endoplasmic reticulum stress, and autophagy deficits in the decline of β-cell mass in Japanese type 2 diabetic patients. Diabetes Care, 37(7): 1966–1974

PMID

76 Montgomery M K, Turner N (2015). Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect, 4(1): R1–R15

PMID

77 Morgan P G, Higdon R, Kolker N, Bauman A T, Ilkayeva O, Newgard C B, Kolker E, Steele L M, Sedensky M M (2015). Comparison of proteomic and metabolomic profiles of mutants of the mitochondrial respiratory chain in Caenorhabditis elegans. Mitochondrion, 20: 95–102

PMID

78 Munday D C, Howell G, Barr J N, Hiscox J A (2014). Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology. The Journal of pharmacy and pharmacology, Muthulakshmi S, Chakrabarti A K, Mukherjee S.(2015) Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of potential role of azelaic acid. J Physiol Biochem, 71(1): 29–42

79 Narbonne H, Paquis-Fluckinger V, Valero R, Heyries L, Pellissier J F, Vialettes B (2004). Gastrointestinal tract symptoms in maternally inherited diabetes and deafness (MIDD). Diabetes Metab, 30(1): 61–66

PMID

80 Neustadt J, Pieczenik S R (2008). Medication-induced mitochondrial damage and disease. Mol Nutr Food Res, 52(7): 780–788

PMID

81 Ng F, Tang B L (2014). Pyruvate dehydrogenase complex (PDC) export from the mitochondrial matrix. Mol Membr Biol, 31(7-8): 207–210

PMID

82 Nieto-Vazquez I, Fernández-Veledo S, de Alvaro C, Rondinone C M, Valverde A M, Lorenzo M (2007). Protein-tyrosine phosphatase 1B-deficient myocytes show increased insulin sensitivity and protection against tumor necrosis factor-α-induced insulin resistance. Diabetes, 56(2): 404–413

PMID

83 Obre E, Rossignol R (2015). Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy. Int J Biochem Cell Biol, 59: 167–181

PMID

84 Pan T, Gao L, Wu G, Shen G, Xie S, Wen H, Yang J, Zhou Y, Tu Z, Qian W (2015). Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer. Biochem Biophys Res Commun, 456(1): 452–458

PMID

85 Patwardhan G A, Beverly L J, Siskind L J (2016). Sphingolipids and mitochondrial apoptosis. J Bioenerg Biomembr, 48(2): 153–168

PMID

86 Pereira S, Breen D M, Naassan A E, Wang P Y, Uchino H, Fantus I G, Carpentier A C, Gutierrez-Juarez R, Brindley D N, Lam T K, Giacca A (2015). In vivo effects of polyunsaturated, monounsaturated, and saturated fatty acids on hepatic and peripheral insulin sensitivity. Metabolism, 64(2): 315–322

PMID

87 Pillai V B, Sundaresan N R, Gupta M P (2014). Regulation of Akt signaling by sirtuins: its implication in cardiac hypertrophy and aging. Circ Res, 114(2): 368–378

PMID

88 Roth M, Chen W Y (2014). Sorting out functions of sirtuins in cancer. Oncogene, 33(13): 1609–1620

PMID

89 Salerno A, Fragasso G, Esposito A, Canu T, Lattuada G, Manzoni G, Del Maschio A, Margonato A, De Cobelli F, Perseghin G (2015). Effects of short-term manipulation of serum FFA concentrations on left ventricular energy metabolism and function in patients with heart failure: no association with circulating bio-markers of inflammation. Acta diabetologica, Sena L A, Chandel N S.(2012) Physiological roles of mitochondrial reactive oxygen species. Mol Cell, 48(2): 158–167

90 Shaikh S R, Sullivan E M, Alleman R J, Brown D A, Zeczycki T N (2014). Increasing mitochondrial membrane phospholipid content lowers the enzymatic activity of electron transport complexes. Biochemistry, 53(35): 5589–5591

PMID

91 Shin S Y, Kim T H, Wu H, Choi Y H, Kim S G (2014). SIRT1 activation by methylene blue, a repurposed drug, leads to AMPK-mediated inhibition of steatosis and steatohepatitis. Eur J Pharmacol, 727: 115–124

PMID

92 Shokouhi S, Haghani K, Borji P, Bakhtiyari S (2015). Association between PGC-1alpha gene polymorphisms and type 2 diabetes risk: a case-control study of an Iranian population. Can J Diabetes, 39(1): 65–72

PMID

93 Smiljanic K, Vanmierlo T, Mladenovic Djordjevic A, Perovic M, Ivkovic S, Lütjohann D, Kanazir S (2014). Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats. Age (Dordr), 36(3): 9654

PMID

94 Song X, Wang B, Lin S, Jing L, Mao C, Xu P, Lv C, Liu W, Zuo J (2014). Astaxanthin inhibits apoptosis in alveolar epithelial cells type II in vivo and in vitro through the ROS-dependent mitochondrial signalling pathway. J Cell Mol Med, 18(11): 2198–2212

PMID

95 Stefanowicz M, Strączkowski M, Karczewska-Kupczewska M (2015). The role of SIRT1 in the pathogenesis of insulin resistance in skeletal muscle. Postepy Hig Med Dosw (Online), 69: 63–68

96 Suter M, Bocock P, Showalter L, Hu M, Shope C, McKnight R, Grove K, Lane R, Aagaard-Tillery K (2011). Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates. FASEB J, 25(2): 714–726

PMID

97 Suzuki Y, Nishimaki K, Taniyama M, Muramatsu T, Atsumi Y, Matsuoka K, Ohta S (2004). Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation. Diabetes Res Clin Pract, 63(3): 225–229

PMID

98 Taheripak G, Bakhtiyari S, Rajabibazl M, Pasalar P, Meshkani R (2013). Protein tyrosine phosphatase 1B inhibition ameliorates palmitate-induced mitochondrial dysfunction and apoptosis in skeletal muscle cells. Free Radic Biol Med, 65: 1435–1446

PMID

99 Tanaka N, Takahashi S, Matsubara T, Jiang C, Sakamoto W, Chanturiya T, Teng R, Gavrilova O, Gonzalez F J (2015). Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice. J Biol Chem, 290(5): 3092–3105

PMID

100 Tanaka N, Takahashi S, Matsubara T, Jiang C, Sakamoto W, Chanturiya T, Teng R, Gavrilova O, Gonzalez F J (2015). Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice. J Biol Chem, 290(5): 3092–3105

PMID

101 Tang X, Shen T, Jiang X, Xia M, Sun X, Guo H, Ling W (2015). Purified anthocyanins from bilberry and black currant attenuate hepatic mitochondrial dysfunction and steatohepatitis in mice with methionine and choline deficiency. J Agric Food Chem, 63(2): 552–561

PMID

102 Taylor E M, Jones A D, Henagan T M (2014). A review of mitochondrial-derived fatty acids in epigenetic regulation of obesity and type 2 diabetes. J Nutrit Health Food Sci, 2(3): 1–4

PMID

103 Tzivion G, Dobson M, Ramakrishnan G (2011). FoxO transcription factors; Regulation by AKT and 14–3-3 proteins. Biochimica et Biophysica Acta (BBA)-. Molecular Cell Research, 1813(11): 1938–1945

104 Udagawa C, Tada N, Asano J, Ishioka K, Ochiai K, Bonkobara M, Tsuchida S, Omi T (2014). The genetic association study between polymorphisms in uncoupling protein 2 and uncoupling protein 3 and metabolic data in dogs. BMC Res Notes, 7(1): 904

PMID

105 Vakili S, Ebrahimi S S S, Sadeghi A, Gorgani-Firuzjaee S, Beigy M, Pasalar P, Meshkani R (2013). Hydrodynamic-based delivery of PTP1B shRNA reduces plasma glucose levels in diabetic mice. Mol Med Rep, 7(1): 211–216

PMID

106 Venediktova N, Shigaeva M, Belova S, Belosludtsev K, Belosludtseva N, Gorbacheva O, Lezhnev E, Lukyanova L, Mironova G (2013). Oxidative phosphorylation and ion transport in the mitochondria of two strains of rats varying in their resistance to stress and hypoxia. Mol Cell Biochem, 383(1-2): 261–269

PMID

107 Villena J A (2014). New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS J, 282(4):647–672

108 Vyssokikh M Y, Antonenko Y N, Lyamzaev K G, Rokitskaya T I, Skulachev V P (2015). Methodology for use of mitochondria-targeted cations in the field of oxidative stress-related research. Mitochondrial Medicine: Volume II, Manipulating Mitochondrial Function, 149–159

109 Wang Q, Sun X, Li X, Dong X, Li P, Zhao L (2015). Resveratrol attenuates intermittent hypoxia-induced insulin resistance in rats: involvement of Sirtuin 1 and the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway. Mol Med Rep, 11(1): 151–158

PMID

110 Wang S P, Yang H, Wu J W, Gauthier N, Fukao T, Mitchell G A (2014). Metabolism as a tool for understanding human brain evolution: lipid energy metabolism as an example. J Hum Evol, 77: 41–49

PMID

111 Wang S P, Yang H, Wu J W, Gauthier N, Fukao T, Mitchell G A (2014). Metabolism as a tool for understanding human brain evolution: lipid energy metabolism as an example. J Hum Evol, 77: 41–49

PMID

112 Williams A S, Kang L, Zheng J, Grueter C, Bracy D P, James F D, Pozzi A, Wasserman D H (2015). Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance. J Biol Chem, 290(10): 6546–6557

PMID

113 Wright E Jr, Scism-Bacon J L, Glass L C (2006). Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int J Clin Pract, 60(3): 308–314

PMID

114 Wuttke A (2015). Lipid signalling dynamics at the β-cell plasma membrane. Basic Clin Pharmacol Toxicol, 116(4): 281–290

PMID

115 Yki-Järvinen H (2005). Fat in the liver and insulin resistance. Ann Med, 37(5): 347–356

PMID

116 Yki-Järvinen H, Westerbacka J (2005). The fatty liver and insulin resistance. Curr Mol Med, 5(3): 287–295

PMID

117 Yu H, Yang Z, Ding X, Wang Y, Han Y (2014). Correlation between the different chain lengths of free fatty acid oxidation and ability of trophoblastic invasion. Chin Med J (Engl), 127(19): 3378–3382

PMID

118 Zabolotny J M, Haj F G, Kim Y B, Kim H J, Shulman G I, Kim J K, Neel B G, Kahn B B (2004). Transgenic overexpression of protein-tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen-related phosphatase does not additively impair insulin action. J Biol Chem, 279(23): 24844–24851

PMID

119 Zhao Y, Ling F, Griffin T M, He T, Towner R, Ruan H, Sun X H (2014). Up-regulation of the Sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor g coactivator-1α (PGC-1α) genes in white adipose tissue of Id1 protein-deficient mice: implications in the protection against diet and age-induced glucose intolerance. J Biol Chem, 289(42): 29112–29122

PMID

120 Zhong H, Yin H (2015). Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol, 4: 193–199

PMID

121 Zhu M, Du J, Chen S, Liu A D, Holmberg L, Chen Y, Zhang C, Tang C, Jin H (2014). L-cystathionine inhibits the mitochondria-mediated macrophage apoptosis induced by oxidized low density lipoprotein. Int J Mol Sci, 15(12): 23059–23073

PMID

122 Zhu M, Du J, Chen S, Liu A D, Holmberg L, Chen Y, Zhang C, Tang C, Jin H (2014). L-cystathionine inhibits the mitochondria-mediated macrophage apoptosis induced by oxidized low density lipoprotein. Int J Mol Sci, 15(12): 23059–23073

PMID