Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury

Zhongze Yuan , Lusen Shi , Xiao-Na Tao , Xiangchuang Fan , Han Zheng , Yifan Shang , Xiaoqing Zhao , Fan Yang , Hui Lin , Peng Xiao , Bo Chu , Jichuan Qiu , Shaohui Zong , Ning Ran , Xiaohong Kong , Jin-Peng Sun , Hengxing Zhou , Shiqing Feng

Bone Research ›› 2026, Vol. 14 ›› Issue (1) : 3

PDF
Bone Research ›› 2026, Vol. 14 ›› Issue (1) :3 DOI: 10.1038/s41413-025-00461-w
Review Article
review-article

Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury

Author information +
History +
PDF

Abstract

Traumatic spinal cord injury (SCI) is a debilitating condition characterized by the impairment of neural circuits, leading to the loss of motor and sensory functions and accompanied by severe complications. Substantial research has reported the therapeutic potential of Omega-3 fatty acids for the central nervous system, particularly after traumatic SCI. Omega-3 fatty acids may contribute to improving SCI recovery through their anti-inflammatory, anti-oxidative, neurotrophic, and membrane integrity-preserving properties. These functions of Omega-3 fatty acids are primarily mediated via the activation of G protein-coupled receptor 120 (GPR120), commonly known as the fish oil-specific receptor. Advancements in understanding of the molecular mechanisms of GPR120’s recognition of Omega-3 fatty acids and its downstream signaling mechanisms has significantly promoted research on the pharmacological potential of Omega-3 fatty acids and the development of highly selective and high-affinity alternatives. This review aims to provide in-depth analysis of the comprehensive therapeutic potential of Omega-3 fatty acids for SCI and its accompanying complications, and the prospects for developing novel drugs based on the recognition of Omega-3 fatty acids by GPR120.

Cite this article

Download citation ▾
Zhongze Yuan, Lusen Shi, Xiao-Na Tao, Xiangchuang Fan, Han Zheng, Yifan Shang, Xiaoqing Zhao, Fan Yang, Hui Lin, Peng Xiao, Bo Chu, Jichuan Qiu, Shaohui Zong, Ning Ran, Xiaohong Kong, Jin-Peng Sun, Hengxing Zhou, Shiqing Feng. Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury. Bone Research, 2026, 14(1): 3 DOI:10.1038/s41413-025-00461-w

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Fan B, Wei Z, Feng S. Progression in translational research on spinal cord injury based on microenvironment imbalance. Bone Res., 2022, 10: 35

[2]

Anderson MA, et al.. Natural and targeted circuit reorganization after spinal cord injury. Nat. Neurosci., 2022, 25: 1584-1596

[3]

Fan B, et al.. Microenvironment imbalance of spinal cord injury. Cell Transplant., 2018, 27: 853-866

[4]

Ahuja CS, et al.. Traumatic spinal cord injury. Nat. Rev. Dis. Prim., 2017, 3 17018

[5]

Freund P, et al.. MRI in traumatic spinal cord injury: from clinical assessment to neuroimaging biomarkers. Lancet Neurol., 2019, 18: 1123-1135

[6]

Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. Neurol.18, 459–480 (2019).

[7]

Kathe C, et al.. The neurons that restore walking after paralysis. Nature, 2022, 611: 540-547

[8]

Guan, C. et al. Stability of motor representations after paralysis. eLife11, e74478 (2022).

[9]

Zheng R, et al.. A critical appraisal of clinical practice guidelines on surgical treatments for spinal cord injury. Spine J., 2023, 23: 1739-1749

[10]

Guan B, et al.. A critical appraisal of clinical practice guidelines on pharmacological treatments for spinal cord injury. Spine J., 2023, 23: 392-402

[11]

Zhou H, et al.. Epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China: a hospital-based retrospective study. Neural Regen. Res., 2024, 19: 1126-1133

[12]

Huang H, et al.. Advances and prospects of cell therapy for spinal cord injury patients. J. Neurorestoratol., 2022, 10: 13-30

[13]

Ma C, Zhang P, Shen Y. Progress in research into spinal cord injury repair: Tissue engineering scaffolds and cell transdifferentiation. J. Neurorestoratol., 2019, 7: 196-206

[14]

Bracken MB, et al.. Administration of methylprednisolone for 24 or 48 h or tirilazad mesylate for 48 h in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA, 1997, 277: 1597-1604

[15]

Roquilly A, et al.. French recommendations for the management of patients with spinal cord injury or at risk of spinal cord injury. Anaesth. Crit. Care Pain. Med., 2020, 39: 279-289

[16]

Liu LJW, Rosner J, Cragg JJ. Journal Club: High-dose methylprednisolone for acute traumatic spinal cord injury: a meta-analysis. Neurology, 2020, 95: 272-274

[17]

Lee JH, et al.. Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury. Exp. Neurol., 2010, 225: 219-230

[18]

Geisler FH, Coleman WP, Grieco G, Poonian D. The Sygen multicenter acute spinal cord injury study. Spine (Philos. Pa 1976), 2001, 26: S87-S98

[19]

Kitzman PH. Effectiveness of riluzole in suppressing spasticity in the spinal cord injured rat. Neurosci. Lett., 2009, 455: 150-153

[20]

Tuszynski MH, et al.. Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury. Exp. Neurol., 1996, 137: 157-173

[21]

Marti-Solano M, et al.. Combinatorial expression of GPCR isoforms affects signalling and drug responses. Nature, 2020, 587: 650-656

[22]

Santos R, et al.. A comprehensive map of molecular drug targets. Nat. Rev. Drug Discov., 2017, 16: 19-34

[23]

Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov., 2017, 16: 829-842

[24]

Fish oil supplements. Jama312, 839-840 (2014).

[25]

Khan I, et al.. Omega-3 long-chain polyunsaturated fatty acids: Metabolism and health implications. Prog. lipid Res., 2023, 92 101255

[26]

Kołodziej Ł, et al.. How fish consumption prevents the development of Major Depressive Disorder? A comprehensive review of the interplay between n-3 PUFAs, LTP and BDNF. Prog. lipid Res., 2023, 92 101254

[27]

Jiang, J. H. et al. Identification of novel acinetobacter baumannii host fatty acid stress adaptation strategies. mBio10, e02056–18 (2019).

[28]

Oh D, et al.. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell, 2010, 142: 687-698

[29]

Yan Y, et al.. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity, 2013, 38: 1154-1163

[30]

Hilgendorf KI, et al.. Omega-3 fatty acids activate ciliary FFAR4 to control adipogenesis. Cell, 2019, 179: 1289-1305.e1221

[31]

Okereke O, et al.. Effect of long-term supplementation with marine omega-3 fatty acids vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. JAMA, 2021, 326: 2385-2394

[32]

Kagan I, et al.. Preemptive enteral nutrition enriched with eicosapentaenoic acid, gamma-linolenic acid and antioxidants in severe multiple trauma: a prospective, randomized, double-blind study. Intensive Care Med., 2015, 41: 460-469

[33]

Billman G, Kang J, Leaf A. Prevention of sudden cardiac death by dietary pure omega-3 polyunsaturated fatty acids in dogs. Circulation, 1999, 99: 2452-2457

[34]

Hu F, Willett W. Optimal diets for prevention of coronary heart disease. JAMA, 2002, 288: 2569-2578

[35]

Rist P, Buring J, Cook N, Manson J, Rexrode K. Effect of vitamin D and/or omega-3 fatty acid supplementation on stroke outcomes: a randomized trial. Eur. J. Neurol., 2021, 28: 809-815

[36]

Vinding R, et al.. Effect of fish oil supplementation in pregnancy on bone, lean, and fat mass at six years: randomised clinical trial. BMJ (Clin. Res. ed.), 2018, 362: k3312

[37]

Mayor S. High dose fish oil supplements in late pregnancy reduce asthma in offspring, finds study. BMJ (Clin. Res. ed.), 2016, 356: i6861

[38]

Oh D, et al.. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat. Med., 2014, 20: 942-947

[39]

Mao C, et al.. Unsaturated bond recognition leads to biased signal in a fatty acid receptor. Science, 2023, 380 eadd6220

[40]

de Carvalho, C. & Caramujo, M. J. The various roles of fatty acids. Molecules23, 2583 (2018).

[41]

Kimura I, Ichimura A, Ohue-Kitano R, Igarashi M. Free fatty acid receptors in health and disease. Physiol. Rev., 2020, 100: 171-210

[42]

D’Angelo, S., Motti, M. L. & Meccariello, R. ω-3 and ω-6 Polyunsaturated fatty acids, obesity and cancer. Nutrients12, 2751 (2020).

[43]

Djuricic, I. & Calder, P. C. Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: an update for 2021. Nutrients13, https://doi.org/10.3390/nu13072421 (2021).

[44]

Nguyen, Q. V., Malau-Aduli, B. S., Cavalieri, J., Malau-Aduli, A. E. O. & Nichols, P. D. Enhancing omega-3 long-chain polyunsaturated fatty acid content of dairy-derived foods for human consumption. Nutrients11, 743 (2019).

[45]

Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacol. Res., 1999, 40: 211-225

[46]

Li, K., Sinclair, A. J., Zhao, F. & Li, D. Uncommon fatty acids and cardiometabolic health. Nutrients10, 1559 (2018).

[47]

Lane K, Derbyshire E, Li W, Brennan C. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Crit. Rev. Food Sci. Nutr., 2014, 54: 572-579

[48]

Shanab SMM, Hafez RM, Fouad AS. A review on algae and plants as potential source of arachidonic acid. J. Adv. Res., 2018, 11: 3-13

[49]

Siriwardhana N, et al.. Modulation of adipose tissue inflammation by bioactive food compounds. J. Nutritional Biochem., 2013, 24: 613-623

[50]

Poggioli R, Hirani K, Jogani VG, Ricordi C. Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders. Eur. Rev. Med. Pharmacol. Sci., 2023, 27: 7380-7400

[51]

Balić, A., Vlašić, D., Žužul, K., Marinović, B. & Bukvić Mokos, Z. Omega-3 versus Omega-6 polyunsaturated fatty acids in the prevention and treatment of inflammatory skin diseases. Int. J. Mol. Sci.21, 741 (2020).

[52]

Saika A, Nagatake T, Kunisawa J. Host- and microbe-dependent dietary lipid metabolism in the control of allergy, inflammation, and immunity. Front. Nutr., 2019, 6: 36

[53]

Kimura, I., Ichimura, A., Ohue-Kitano, R. & Igarashi, M. J. A. P. S. B., MD. Free fatty acid receptors in health and disease. Physiol. Rev. 100, 171–210 (2020).

[54]

Liu J, Lv Z, Li H. Upregulation of G-protein coupled receptor 120 in rats following spinal cord injury. Neurochem. Res, 2022, 47: 921-932

[55]

Milligan G, Alvarez-Curto E, Hudson BD, Prihandoko R, Tobin AB. FFA4/GPR120: pharmacology and therapeutic opportunities. Trends Pharmacol. Sci., 2017, 38: 809-821

[56]

Wang Y, Liu H, Zhang Z. Recent advance in regulatory effect of GRP120 on bone metabolism. Aging Dis., 2023, 14: 1714-1727

[57]

Zhang X, Macielag MJ. GPR120 agonists for the treatment of diabetes: a patent review (2014 present). Expert Opin. Ther. Pat., 2020, 30: 729-742

[58]

Gensel JC, Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res., 2015, 1619: 1-11

[59]

Lee CY, Chooi WH, Ng SY, Chew SY. Modulating neuroinflammation through molecular, cellular and biomaterial-based approaches to treat spinal cord injury. Bioeng. Transl. Med., 2023, 8 e10389

[60]

Zhou X, et al.. Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2. Nat. Neurosci., 2020, 23: 337-350

[61]

Van Broeckhoven J, Sommer D, Dooley D, Hendrix S, Franssen A. Macrophage phagocytosis after spinal cord injury: when friends become foes. Brain J. Neurol., 2021, 144: 2933-2945

[62]

David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat. Rev. Neurosci., 2011, 12: 388-399

[63]

Yong V, Rivest S. Taking advantage of the systemic immune system to cure brain diseases. Neuron, 2009, 64: 55-60

[64]

Shechter R, et al.. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med., 2009, 6: e1000113

[65]

Gadani SP, Walsh JT, Lukens JR, Kipnis J. Dealing with danger in the CNS: the response of the immune system to injury. Neuron, 2015, 87: 47-62

[66]

Gong T, Liu L, Jiang W, Zhou R. DAMP-sensing receptors in sterile inflammation and inflammatory diseases. Nat. Rev. Immunol., 2020, 20: 95-112

[67]

Hu X, et al.. Spinal cord injury: molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther., 2023, 8: 245

[68]

Hellenbrand DJ, et al.. Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration. J. Neuroinflammation, 2021, 18 284

[69]

Norden DM, et al.. Bone marrow-derived monocytes drive the inflammatory microenvironment in local and remote regions after thoracic spinal cord injury. J. Neurotrauma, 2019, 36: 937-949

[70]

Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet, 1999, 354: 447-455

[71]

Manson JE, et al.. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N. Engl. J. Med., 2019, 380: 23-32

[72]

Wei BZ, Li L, Dong CW, Tan CC, Xu W. The Relationship of omega-3 fatty acids with dementia and cognitive decline: evidence from prospective cohort studies of supplementation, dietary intake, and blood markers. Am. J. Clin. Nutr., 2023, 117: 1096-1109

[73]

Hill CL, et al.. Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose. Ann. Rheum. Dis., 2016, 75: 23-29

[74]

Jobin, M. L. et al. Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling. Mol. Psychiatry28, 1960–1969 (2023).

[75]

Wood AHR, Chappell HF, Zulyniak MA. Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer’s disease. Eur. J. Nutr., 2022, 61: 589-604

[76]

Custers, Emma EM, Kiliaan, Amanda J. Dietary lipids from body to brain. Prog. lipid Res., 2022, 85 101144

[77]

Layé S, Nadjar A, Joffre C, Bazinet R. Anti-inflammatory effects of omega-3 fatty acids in the brain: physiological mechanisms and relevance to pharmacology. Pharmacol. Rev., 2018, 70: 12-38

[78]

Fernandez, R. et al. Acyl-CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging. JCI Insight6, e144351 (2021).

[79]

Wellhauser L, Belsham D. Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J. Neuroinflammation, 2014, 11 60

[80]

Chang P, Khatchadourian A, McKinney R, Maysinger D. Docosahexaenoic acid (DHA): a modulator of microglia activity and dendritic spine morphology. J. Neuroinflammation, 2015, 12 34

[81]

Mori M, et al.. Neuroprotective effect of omega-3 polyunsaturated fatty acids in the 6-OHDA model of Parkinson’s disease is mediated by a reduction of inducible nitric oxide synthase. Nutritional Neurosci., 2018, 21: 341-351

[82]

Bailes, J. E. et al. Omega-3 fatty acid supplementation in severe brain trauma: case for a large multicenter trial. J. Neurosurg. 133, 598–602 (2020).

[83]

Jiang X, et al.. A post-stroke therapeutic regimen with omega-3 polyunsaturated fatty acids that promotes white matter integrity and beneficial microglial responses after cerebral ischemia. Transl. stroke Res., 2016, 7: 548-561

[84]

Baazm, M., Behrens, V., Beyer, C., Nikoubashman, O. & Zendedel, A. Regulation of inflammasomes by application of omega-3 polyunsaturated fatty acids in a spinal cord injury model. Cells10, 3147 (2021).

[85]

Bi J, et al.. Neuroprotective effect of omega-3 fatty acids on spinal cord injury induced rats. Brain Behav., 2019, 9 e01339

[86]

Paterniti I, et al.. Docosahexaenoic acid attenuates the early inflammatory response following spinal cord injury in mice: in-vivo and in-vitro studies. J. Neuroinflammation, 2014, 11 6

[87]

Huang WL, et al.. A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain J. Neurol., 2007, 130: 3004-3019

[88]

Lim SN, Huang W, Hall JC, Michael-Titus AT, Priestley JV. Improved outcome after spinal cord compression injury in mice treated with docosahexaenoic acid. Exp. Neurol., 2013, 239: 13-27

[89]

Trépanier MO, Hopperton KE, Orr SK, Bazinet RP. N-3 polyunsaturated fatty acids in animal models with neuroinflammation: an update. Eur. J. Pharmacol., 2016, 785: 187-206

[90]

Madore C, et al.. Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes. Brain Behav., Immun., 2014, 41: 22-31

[91]

Kang JX, Wang J, Wu L, Kang ZB. Transgenic mice: fat-1 mice convert n-6 to n-3 fatty acids. Nature, 2004, 427: 504

[92]

Lim SN, et al.. Transgenic mice with high endogenous omega-3 fatty acids are protected from spinal cord injury. Neurobiol. Dis., 2013, 51: 104-112

[93]

Fujieda Y, et al.. Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats. PLoS one, 2012, 7: e43152

[94]

Figueroa JD, et al.. Fatty acid binding protein 5 modulates docosahexaenoic acid-induced recovery in rats undergoing spinal cord injury. J. Neurotrauma, 2016, 33: 1436-1449

[95]

López-Vales R, et al.. Fenretinide promotes functional recovery and tissue protection after spinal cord contusion injury in mice. J. Neurosci. J. Soc. Neurosci., 2010, 30: 3220-3226

[96]

Allison DJ, Beaudry KM, Thomas AM, Josse AR, Ditor DS. Changes in nutrient intake and inflammation following an anti-inflammatory diet in spinal cord injury. J. Spinal Cord. Med, 2019, 42: 768-777

[97]

Norouzi Javidan A, et al.. Does consumption of polyunsaturated fatty acids influence on neurorehabilitation in traumatic spinal cord-injured individuals? A double-blinded clinical trial. Spinal cord., 2014, 52: 378-382

[98]

Ong, G. & Logue, S. E. Unfolding the interactions between endoplasmic reticulum stress and oxidative stress. Antioxidants12, 981 (2023).

[99]

Yu M, et al.. Oxidative stress following spinal cord injury: from molecular mechanisms to therapeutic targets. J. Neurosci. Res., 2023, 101: 1538-1554

[100]

Hollyfield J, et al.. Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat. Med., 2008, 14: 194-198

[101]

Geng Y, et al.. Recent progress in the development of fluorescent probes for imaging pathological oxidative stress. Chem. Soc. Rev., 2023, 52: 3873-3926

[102]

Singh V, Ubaid S. Role of silent information regulator 1 (SIRT1) in regulating oxidative stress and inflammation. Inflammation, 2020, 43: 1589-1598

[103]

Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid. Med. Cell. Longev., 2014, 2014 102158

[104]

Shchepinov MS. Polyunsaturated fatty acid deuteration against neurodegeneration. Trends Pharmacol. Sci., 2020, 41: 236-248

[105]

Xiong T, et al.. Multifunctional integrated nanozymes facilitate spinal cord regeneration by remodeling the extrinsic neural environment. Adv. Sci., 2023, 10 e2205997

[106]

King VR, et al.. Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J. Neurosci. J. Soc. Neurosci., 2006, 26: 4672-4680

[107]

Figueroa JD, De Leon M. Neurorestorative targets of dietary long-chain omega-3 fatty acids in neurological injury. Mol. Neurobiol., 2014, 50: 197-213

[108]

He, L., Ye, J., Zhuang, X., Shi, J. & Wu, W. Omega-3 polyunsaturated fatty acids alleviate endoplasmic reticulum stress-induced neuroinflammation by protecting against traumatic spinal cord injury through the histone deacetylase 3/ peroxisome proliferator-activated receptor-γ coactivator pathway. J. Neuropathol. Exp. Neurol. 83, 939–950 (2024).

[109]

Tran A, Warren P, Silver J. The biology of regeneration failure and success after spinal cord injury. Physiol. Rev., 2018, 98: 881-917

[110]

Clifford, T., Finkel, Z., Rodriguez, B., Joseph, A. & Cai, L. Current advancements in spinal cord injury research-glial scar formation and neural regeneration. Cells12, 853 (2023).

[111]

Czepiel M, Boddeke E, Copray S. Human oligodendrocytes in remyelination research. Glia, 2015, 63: 513-530

[112]

Duncan GJ, et al.. The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury. Glia, 2020, 68: 227-245

[113]

Zheng B, Tuszynski MH. Regulation of axonal regeneration after mammalian spinal cord injury. Nat. Rev. Mol. Cell Biol., 2023, 24: 396-413

[114]

Zhou T, et al.. Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury. Nat. Neurosci., 2019, 22: 421-435

[115]

Britten-Jones AC, Craig JP, Downie LE. Omega-3 polyunsaturated fatty acids and corneal nerve health: current evidence and future directions. Ocul. Surf., 2023, 27: 1-12

[116]

Song C, Wang H. Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 2011, 35: 760-768

[117]

Liu ZH, Yip PK, Priestley JV, Michael-Titus AT. A single dose of docosahexaenoic acid increases the functional recovery promoted by rehabilitation after cervical spinal cord injury in the rat. J. neurotrauma, 2017, 34: 1766-1777

[118]

Pekny M, Pekna M. Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol. Rev., 2014, 94: 1077-1098

[119]

Adams KL, Gallo V. The diversity and disparity of the glial scar. Nat. Neurosci., 2018, 21: 9-15

[120]

Blondeau N, et al.. Subchronic alpha-linolenic acid treatment enhances brain plasticity and exerts an antidepressant effect: a versatile potential therapy for stroke. Neuropsychopharmacol. Publ. Am. Coll. Neuropsychopharmacol., 2009, 34: 2548-2559

[121]

Kemse N, Kale A, Chavan-Gautam P, Joshi S. Increased intake of vitamin B, folate, and omega-3 fatty acids to improve cognitive performance in offspring born to rats with induced hypertension during pregnancy. Food Funct., 2018, 9: 3872-3883

[122]

Keefe, K. M., Sheikh, I. S. & Smith, G. M. Targeting neurotrophins to specific populations of neurons: NGF, BDNF, and NT-3 and their relevance for treatment of spinal cord injury. Int. J. Mol. Sci.18, 548 (2017).

[123]

Holly LT, et al.. Dietary therapy to promote neuroprotection in chronic spinal cord injury. J. Neurosurg. Spine, 2012, 17: 134-140

[124]

Liu ZH, et al.. A single bolus of docosahexaenoic acid promotes neuroplastic changes in the innervation of spinal cord interneurons and motor neurons and improves functional recovery after spinal cord injury. J. Neurosci. J. Soc. Neurosci., 2015, 35: 12733-12752

[125]

Billman GE. The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: a critical reassessment. Pharmacol. Therapeutics, 2013, 140: 53-80

[126]

Zhao Z, et al.. Docosahexaenoic acid reduces the incidence of early afterdepolarizations caused by oxidative stress in rabbit ventricular myocytes. Front. Physiol., 2012, 3: 252

[127]

Saini RK, Keum YS. Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance—a review. Life Sci., 2018, 203: 255-267

[128]

Michael-Titus AT, Priestley JV. Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity?. Trends Neurosci., 2014, 37: 30-38

[129]

Vreugdenhil M, et al.. Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons. Proc. Natl. Acad. Sci. USA, 1996, 93: 12559-12563

[130]

Heurteaux C, et al.. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J., 2004, 23: 2684-2695

[131]

Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science, 2010, 327: 46-50

[132]

Kim W, et al.. n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation. J. Immunol., 2008, 181: 6236-6243

[133]

Wada J, Makino H. Innate immunity in diabetes and diabetic nephropathy. Nat. Rev. Nephrol., 2016, 12: 13-26

[134]

De Smedt-Peyrusse V, et al.. Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in microglial cells by inhibiting lipopolysaccharide receptor presentation but not its membrane subdomain localization. J. Neurochem., 2008, 105: 296-307

[135]

Payrits, M. et al. Resolvin D1 and D2 inhibit transient receptor potential vanilloid 1 and ankyrin 1 ion channel activation on sensory neurons via lipid raft modification. Int. J. Mol. Sci.21, 5019 (2020).

[136]

Kim J, et al.. Resolvin D3 promotes inflammatory resolution, neuroprotection, and functional recovery after spinal cord injury. Mol. Neurobiol., 2021, 58: 424-438

[137]

Raker VK, Becker C, Steinbrink K. The cAMP pathway as therapeutic target in autoimmune and inflammatory diseases. Front. Immunol., 2016, 7: 123

[138]

Lee JW, et al.. Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function. Nat. Commun., 2016, 7 13123

[139]

Kim HY, Spector AA. N-Docosahexaenoylethanolamine: a neurotrophic and neuroprotective metabolite of docosahexaenoic acid. Mol. Asp. Med., 2018, 64: 34-44

[140]

Bäck M. Icosapent ethyl in cardiovascular prevention: resolution of inflammation through the eicosapentaenoic acid-resolvin E1-ChemR23 axis. Pharmacol. Ther., 2023, 247 108439

[141]

Lee HN, Surh YJ. Therapeutic potential of resolvins in the prevention and treatment of inflammatory disorders. Biochem. Pharmacol., 2012, 84: 1340-1350

[142]

Liu G, et al.. Neuronal phagocytosis by inflammatory macrophages in ALS spinal cord: inhibition of inflammation by resolvin D1. Am. J. Neurodegener. Dis., 2012, 1: 60-74

[143]

Park CK, et al.. Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: distinct roles of resolvin D1, D2, and E1. J. Neurosci. J. Soc. Neurosci., 2011, 31: 18433-18438

[144]

Pan Y, et al.. Fatty acid-binding protein 5 at the blood-brain barrier regulates endogenous brain docosahexaenoic acid levels and cognitive function. J. Neurosci. J. Soc. Neurosci., 2016, 36: 11755-11767

[145]

Xu S, Jay A, Brunaldi K, Huang N, Hamilton JA. CD36 enhances fatty acid uptake by increasing the rate of intracellular esterification but not transport across the plasma membrane. Biochemistry, 2013, 52: 7254-7261

[146]

Ochiai Y, et al.. The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport. J. Neurochem., 2017, 141: 400-412

[147]

Lin T, et al.. A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats. Bone Res., 2015, 3 15028

[148]

Ushida T, et al.. Mirogabalin for central neuropathic pain after spinal cord injury: a randomized, double-blind, placebo-controlled, phase 3 study in Asia. Neurology, 2023, 100: e1193-e1206

[149]

Dionyssiotis Y, et al.. Sarcopenic obesity in individuals with neurodisabilities: the SarcObeNDS Study. Front. Endocrinol., 2022, 13 868298

[150]

Raguindin, P. et al. Body composition according to spinal cord injury level: a systematic review and meta-analysis. J. Clin. Med.10, 3911 (2021).

[151]

Lin Z, et al.. Cardiovascular benefits of fish-oil supplementation against fine particulate air pollution in China. J. Am. Coll. Cardiol., 2019, 73: 2076-2085

[152]

Fu Y, et al.. Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity. Mediators Inflamm., 2021, 2021 8879227

[153]

Jensen M, Chodroff M, Dworkin R. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology, 2007, 68: 1178-1182

[154]

Figueroa JD, et al.. Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury. Neuroscience, 2013, 255: 1-18

[155]

Hama A, Sagen J. Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain. Brain Res., 2011, 1412: 44-54

[156]

Finnerup NB, Baastrup C. Spinal cord injury pain: mechanisms and management. Curr. Pain. Headache Rep., 2012, 16: 207-216

[157]

Xu ZZ, Berta T, Ji RR. Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury. J. Neuroimmune Pharm., 2013, 8: 37-41

[158]

Unda SR, Villegas EA, Toledo ME, Asis Onell G, Laino CH. Beneficial effects of fish oil enriched in omega-3 fatty acids on the development and maintenance of neuropathic pain. J. Pharm. Pharm., 2020, 72: 437-447

[159]

Durán AM, et al.. Effects of omega-3 polyunsaturated fatty-acid supplementation on neuropathic pain symptoms and sphingosine levels in Mexican-Americans with type 2 diabetes. Diab Metab. Syndr. Obes., 2019, 12: 109-120

[160]

Yorek MA. The potential role of fatty acids in treating diabetic neuropathy. Curr. Diab Rep., 2018, 18 86

[161]

Redivo DDB, Jesus CHA, Sotomaior BB, Gasparin AT, Cunha JM. Acute antinociceptive effect of fish oil or its major compounds, eicosapentaenoic and docosahexaenoic acids on diabetic neuropathic pain depends on opioid system activation. Behav. Brain Res., 2019, 372 111992

[162]

Motter AL, Ahern GP. TRPA1 is a polyunsaturated fatty acid sensor in mammals. PLoS One, 2012, 7: e38439

[163]

Skerratt SE, West CW. Ion channel therapeutics for pain. Channels, 2015, 9: 344-351

[164]

Ko GD, Nowacki NB, Arseneau L, Eitel M, Hum A. Omega-3 fatty acids for neuropathic pain: case series. Clin. J. Pain., 2010, 26: 168-172

[165]

Ensrud KE, Crandall CJ. Osteoporosis. Ann. Intern. Med., 2017, 167: Itc17-itc32

[166]

Craven, B., Cirnigliaro, C., Carbone, L., Tsang, P. & Morse, L. The pathophysiology, identification and management of fracture risk, sublesional osteoporosis and fracture among adults with spinal cord injury. J. Personalized Med.13, 966 (2023).

[167]

Garland DE, Adkins RH, Stewart CA. Five-year longitudinal bone evaluations in individuals with chronic complete spinal cord injury. J. Spinal Cord. Med., 2008, 31: 543-550

[168]

Abdelrahman, S., Ireland, A., Winter, M. E., Purcell, M. & Coupaud, S. Osteoporosis after spinal cord injury: aetiology, effects and therapeutic approaches. J Musculoskelet Neuronal Interact.21, 26–50 (2021)

[169]

Tan, C. O., Battaglino, R. A. & Morse, L. R. Spinal cord injury and osteoporosis: causes, mechanisms, and rehabilitation strategies. Int. J. Phys. Med. Rehabil.1, 127 (2013).

[170]

Morse LR, et al.. Osteoporotic fractures and hospitalization risk in chronic spinal cord injury. Osteoporos. Int., 2009, 20: 385-392

[171]

Hachem LD, Ahuja CS, Fehlings MG. Assessment and management of acute spinal cord injury: From point of injury to rehabilitation. J. Spinal Cord. Med., 2017, 40: 665-675

[172]

Haider IT, Lobos SM, Simonian N, Schnitzer TJ, Edwards WB. Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time. Osteoporos. Int., 2018, 29: 2703-2715

[173]

Chantraine A, Nusgens B, Lapiere CM. Bone remodeling during the development of osteoporosis in paraplegia. Calcif. Tissue Int., 1986, 38: 323-327

[174]

Minaire P, et al.. Quantitative histological data on disuse osteoporosis: comparison with biological data. Calcif. Tissue Res., 1974, 17: 57-73

[175]

Zehnder Y, et al.. Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men. Osteoporos. Int., 2004, 15: 180-189

[176]

Szollar SM, Martin EM, Sartoris DJ, Parthemore JG, Deftos LJ. Bone mineral density and indexes of bone metabolism in spinal cord injury. Am. J. Phys. Med. Rehabil., 1998, 77: 28-35

[177]

Shams, R. et al. The pathophysiology of osteoporosis after spinal cord injury. Int. J. Mol. Sci.22, 3057 (2021).

[178]

de Groen P, et al.. Esophagitis associated with the use of alendronate. N. Engl. J. Med., 1996, 335: 1016-1021

[179]

Lerner UH. Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis. J. Dent. Res., 2006, 85: 596-607

[180]

Watkins BA, Lippman HE, Le Bouteiller L, Li Y, Seifert MF. Bioactive fatty acids: role in bone biology and bone cell function. Prog. Lipid Res., 2001, 40: 125-148

[181]

Sun D, et al.. Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J. Bone Miner. Res., 2003, 18: 1206-1216

[182]

Watkins BA, Shen CL, Allen KG, Seifert MF. Dietary (n-3) and (n-6) polyunsaturates and acetylsalicylic acid alter ex vivo PGE2 biosynthesis, tissue IGF-I levels, and bone morphometry in chicks. J. Bone Miner. Res., 1996, 11: 1321-1332

[183]

Hasturk H, et al.. RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. Faseb J., 2006, 20: 401-403

[184]

Levental KR, et al.. ω-3 polyunsaturated fatty acids direct differentiation of the membrane phenotype in mesenchymal stem cells to potentiate osteogenesis. Sci. Adv., 2017, 3 eaao1193

[185]

Haag M, Magada ON, Claassen N, Böhmer LH, Kruger MC. Omega-3 fatty acids modulate ATPases involved in duodenal Ca absorption. Prostaglandins Leukotrienes, Essent. Fat. Acids, 2003, 68: 423-429

[186]

Kishikawa A, et al.. Docosahexaenoic acid inhibits inflammation-induced osteoclast formation and bone resorption in vivo through GPR120 by inhibiting TNF-α production in macrophages and directly inhibiting osteoclast formation. Front. Endocrinol., 2019, 10: 157

[187]

Ahn SH, et al.. Free fatty acid receptor 4 (GPR120) stimulates bone formation and suppresses bone resorption in the presence of elevated N-3 fatty acid levels. Endocrinology, 2016, 157: 2621-2635

[188]

Sithole, C., Pieterse, C., Howard, K. & Kasonga, A. GPR120 Inhibits RANKL-induced osteoclast formation and resorption by attenuating reactive oxygen species production in RAW264.7 murine macrophages. Int. J. Mol. Sci.22, 10544 (2021).

[189]

Sabour H, et al.. The effects of n-3 fatty acids on inflammatory cytokines in osteoporotic spinal cord injured patients: a randomized clinical trial. J. Res. Med. Sci., 2012, 17: 322-327

[190]

Dodin S, et al.. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J. Clin. Endocrinol. Metab., 2005, 90: 1390-1397

[191]

Ishimoto, R. et al. Prevalence of sarcopenic obesity and factors influencing body composition in persons with spinal cord injury in Japan. Nutrients15, 473 (2023).

[192]

Gater DRJr.. Obesity after spinal cord injury. Phys. Med. Rehabil. Clin. North Am., 2007, 18: 333-351 vii

[193]

Gaudet AD, et al.. Spinal cord injury in rats dysregulates diurnal rhythms of fecal output and liver metabolic indicators. J. Neurotrauma, 2019, 36: 1923-1934

[194]

Cruz-Antonio L, Flores-Murrieta FJ, García-Löpez P, Guízar-Sahagún G, Castañeda-Hernández G. Understanding drug disposition alterations induced by acute spinal cord injury: role of injury level and route of administration for agents submitted to extensive liver metabolism. J. Neurotrauma, 2006, 23: 75-85

[195]

Liu XH, et al.. Spinal cord injury reduces serum levels of fibroblast growth factor-21 and impairs its signaling pathways in liver and adipose tissue in mice. Front. Endocrinol., 2021, 12 668984

[196]

Buchholz AC, Pencharz PB. Energy expenditure in chronic spinal cord injury. Curr. Opin. Clin. Nutr. Metab. Care, 2004, 7: 635-639

[197]

McMillan DW, Bigford GE, Farkas GJ. The physiology of neurogenic obesity: lessons from spinal cord injury research. Obes. Facts, 2023, 16: 313-325

[198]

Gater DRJr., Farkas GJ, Tiozzo E. Pathophysiology of neurogenic obesity after spinal cord injury. Top. Spinal Cord. Inj. Rehabil., 2021, 27: 1-10

[199]

Spungen AM, et al.. Factors influencing body composition in persons with spinal cord injury: a cross-sectional study. J. Appl. Physiol., 2003, 95: 2398-2407

[200]

Sorenson MR. Body composition of women and men with complete motor paraplegia. J. Spinal Cord. Med., 2014, 37: 366-367

[201]

Jones LM, Legge M, Goulding A. Healthy body mass index values often underestimate body fat in men with spinal cord injury. Arch. Phys. Med. Rehabil., 2003, 84: 1068-1071

[202]

Yarar-Fisher C, Chen Y, Jackson AB, Hunter GR. Body mass index underestimates adiposity in women with spinal cord injury. Obesity, 2013, 21: 1223-1225

[203]

Pelletier CA, Miyatani M, Giangregorio L, Craven BC. Sarcopenic obesity in adults with spinal cord injury: a cross-sectional study. Arch. Phys. Med. Rehabil., 2016, 97: 1931-1937

[204]

Felix ER, Gater DRJr.. Interrelationship of neurogenic obesity and chronic neuropathic pain in persons with spinal cord injury. Top. Spinal Cord. Inj. Rehabil., 2021, 27: 75-83

[205]

Gordon PS, Farkas GJ, Gater DRJr.. Neurogenic obesity-induced insulin resistance and type 2 diabetes mellitus in chronic spinal cord injury. Top. Spinal Cord. Inj. Rehabil., 2021, 27: 36-56

[206]

Shojaei MH, Alavinia SM, Craven BC. Management of obesity after spinal cord injury: a systematic review. J. Spinal Cord. Med., 2017, 40: 783-794

[207]

Hotamisligil GS. Inflammation and metabolic disorders. Nature, 2006, 444: 860-867

[208]

Kalupahana N, Goonapienuwala B, Moustaid-Moussa N. Omega-3 fatty acids and adipose tissue: inflammation and browning. Annu. Rev. Nutr., 2020, 40: 25-49

[209]

Titos E, Clària J. Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation. Prostaglandins Other Lipid Mediat., 2013, 107: 77-84

[210]

Kalupahana NS, et al.. Eicosapentaenoic acid prevents and reverses insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation. J. Nutr., 2010, 140: 1915-1922

[211]

Martínez-Fernández L, Laiglesia LM, Huerta AE, Martínez JA, Moreno-Aliaga MJ. Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins Other Lipid Mediat, 2015, 121: 24-41

[212]

Gao H, Geng T, Huang T, Zhao Q. Fish oil supplementation and insulin sensitivity: a systematic review and meta-analysis. Lipids Health Dis., 2017, 16: 131

[213]

Albracht-Schulte K, et al.. Omega-3 fatty acids in obesity and metabolic syndrome: a mechanistic update. J. Nutr. Biochem., 2018, 58: 1-16

[214]

Parra D, et al.. A diet rich in long chain omega-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss. Appetite, 2008, 51: 676-680

[215]

Thorsdottir I, et al.. Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content. Int. J. Obes., 2007, 31: 1560-1566

[216]

Lagerström MC, Schiöth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov., 2008, 7: 339-357

[217]

Cohen, J. et al. Recent research trends in neuroinflammatory and neurodegenerative disorders. Cells13, 511 (2024).

[218]

Poniatowski Ł, et al.. Analysis of the role of CX3CL1 (Fractalkine) and its receptor CX3CR1 in traumatic brain and spinal cord injury: insight into recent advances in actions of neurochemokine agents. Mol. Neurobiol., 2017, 54: 2167-2188

[219]

Goode-Romero G, Dominguez L. Computational study of the conformational ensemble of CX3C chemokine receptor 1 (CX3CR1) and its interactions with antagonist and agonist ligands. J. Mol. Graph. Model., 2022, 117 108278

[220]

Radulovic M, Yoon H, Wu J, Mustafa K, Scarisbrick IA. Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury. Neurobiol. Dis., 2016, 93: 226-242

[221]

Radulovic M, et al.. Genetic targeting of protease activated receptor 2 reduces inflammatory astrogliosis and improves recovery of function after spinal cord injury. Neurobiol. Dis., 2015, 83: 75-89

[222]

Lin B, et al.. GPR34 senses demyelination to promote neuroinflammation and pathologies. Cell. Mol. Immunol., 2024, 21: 1131-1144

[223]

Apweiler M, et al.. Modulation of neuroinflammation and oxidative stress by targeting GPR55-new approaches in the treatment of psychiatric disorders. Mol. Psychiatry, 2024, 29: 3779-3788

[224]

Sayo A, et al.. GPR34 in spinal microglia exacerbates neuropathic pain in mice. J. Neuroinflammation, 2019, 16 82

[225]

Jiang W, Yu W, Tan Y. Activation of GPR55 alleviates neuropathic pain and chronic inflammation. Biotechnol. Appl. Biochem., 2025, 72: 196-206

[226]

Purcell RH, Hall RA. Adhesion G protein-coupled receptors as drug targets. Annu. Rev. Pharm. Toxicol., 2018, 58: 429-449

[227]

Bassilana F, Nash M, Ludwig MG. Adhesion G protein-coupled receptors: opportunities for drug discovery. Nat. Rev. Drug Discov., 2019, 18: 869-884

[228]

Zheng, Y. et al. Development of an allosteric adhesion GPCR nanobody with therapeutic potential. Nat. Chem. Biol.21, 1519–1530 (2025).

[229]

Uniyal A, et al.. Targeting sensory neuron GPCRs for peripheral neuropathic pain. Trends Pharmacol. Sci., 2023, 44: 1009-1027

[230]

Yosten GL, et al.. GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents. J. Clin. Invest., 2020, 130: 2587-2592

[231]

Pondelick AM, et al.. Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1P(1) receptor-mediated G-protein activation in a mouse model of sciatic nerve injury. Neuropharmacology, 2024, 261 110165

[232]

Birgbauer E. Lysophospholipid receptors in neurodegeneration and neuroprotection. Exploration Neuroprotective Ther., 2024, 4: 349-365

[233]

Rich K, Rehman S, Jerman J, Wilkinson G. Investigating the potential of GalR2 as a drug target for neuropathic pain. Neuropeptides, 2023, 98 102311

[234]

Chung HJ, Kim JD, Kim KH, Jeong NY. G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain. Korean J. Anesthesiol., 2014, 66: 230-236

[235]

Holmes FE, et al.. Targeted disruption of the orphan receptor Gpr151 does not alter pain-related behaviour despite a strong induction in dorsal root ganglion expression in a model of neuropathic pain. Mol. Cell. Neurosci., 2017, 78: 35-40

[236]

Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by beta-arrestins. Science, 2005, 308: 512-517

[237]

Shang P, et al.. Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Cell, 2023, 186: 5347-5362.e5324

[238]

Yang F, et al.. Structure, function and pharmacology of human itch receptor complexes. Nature, 2021, 600: 164-169

[239]

Wang JL, et al.. Functional screening and rational design of compounds targeting GPR132 to treat diabetes. Nat. Metab., 2023, 5: 1726-1746

[240]

Xu F, et al.. Identification and target-pathway deconvolution of FFA4 agonists with anti-diabetic activity from Arnebia euchroma (Royle) Johnst. Pharmacol. Res., 2021, 163 105173

[241]

Oh DY, Olefsky JM. G protein-coupled receptors as targets for anti-diabetic therapeutics. Nat. Rev. Drug Discov., 2016, 15: 161-172

[242]

Di Petrillo A, Kumar A, Onali S, Favale A, Fantini MC. GPR120/FFAR4: a potential new therapeutic target for inflammatory bowel disease. Inflamm. bowel Dis., 2023, 29: 1981-1989

[243]

Tanaka T, et al.. Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic beta cells. Naunyn-Schmiedeberg’s. Arch. Pharmacol., 2008, 377: 515-522

[244]

Gagnon J, Anini Y. Glucagon stimulates ghrelin secretion through the activation of MAPK and EPAC and potentiates the effect of norepinephrine. Endocrinology, 2013, 154: 666-674

[245]

Engelstoft MS, et al.. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol. Metab., 2013, 2: 376-392

[246]

Stone VM, et al.. GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia, 2014, 57: 1182-1191

[247]

Cho YM, Kieffer TJ. K-cells and glucose-dependent insulinotropic polypeptide in health and disease. Vitam. Hormones, 2010, 84: 111-150

[248]

Du YQ, et al.. Endogenous Lipid-GPR120 Signaling Modulates Pancreatic Islet Homeostasis to Different Extents. Diabetes, 2022, 71: 1454-1471

[249]

Feng X, Wu CY, Burton FH, Loh HH, Wei LN. β-arrestin protects neurons by mediating endogenous opioid arrest of inflammatory microglia. Cell Death Differ., 2014, 21: 397-406

[250]

Du RW, Du RH, Bu WG. β-Arrestin 2 mediates the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells. J. NeuroImmune Pharmacol. J. Soc. NeuroImmune Pharmacol., 2014, 9: 582-590

[251]

Moniri NH. Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders. Biochem. Pharmacol., 2016, 110-111: 1-15

[252]

Ichimura A, et al.. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature, 2012, 483: 350-354

[253]

Yore MM, et al.. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell, 2014, 159: 318-332

[254]

Elnagdy, M., Barve, S., McClain, C. & Gobejishvili, L. cAMP signaling in pathobiology of alcohol associated liver disease. Biomolecules10, 1433 (2020).

[255]

Secor JD, Fligor SC, Tsikis ST, Yu LJ, Puder M. Free fatty acid receptors as mediators and therapeutic targets in liver disease. Front. Physiol., 2021, 12 656441

[256]

Wang M, Ma LJ, Yang Y, Xiao Z, Wan JB. n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: a critical review. Crit. Rev. Food Sci. Nutr., 2019, 59: S116-s129

[257]

Liu H, et al.. DrugCombDB: a comprehensive database of drug combinations toward the discovery of combinatorial therapy. Nucleic Acids Res., 2020, 48: D871-D881

[258]

Zhang Y, et al.. Versatile metal-phenolic network nanoparticles for multitargeted combination therapy and magnetic resonance tracing in glioblastoma. Biomaterials, 2021, 278 121163

[259]

Kirchhof P, et al.. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference ‘research perspectives in AF. Eur. heart J., 2009, 30: 2969-2977c

[260]

Oliveros G, et al.. Repurposing ibudilast to mitigate Alzheimer’s disease by targeting inflammation. Brain J. Neurol., 2023, 146: 898-911

[261]

Ma Y, et al.. Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses. Chem. Soc. Rev., 2021, 50: 4514-4540

[262]

Figueroa JD, Cordero K, Llán MS, De Leon M. Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury. J. Neurotrauma, 2013, 30: 853-868

[263]

Cholewski, M., Tomczykowa, M. & Tomczyk, M. A Comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients10, 1662 (2018).

[264]

Pan, M. et al. Dietary ω-3 polyunsaturated fatty acids are protective for myopia. Proceedings of the National Academy of Sciences of the United States of America118, e2104689118 (2021).

[265]

Tveit KS, et al.. A randomized, double-blind, placebo-controlled clinical study to investigate the efficacy of herring roe oil for treatment of psoriasis. Acta Derm. Venereologica, 2020, 100: adv00154

[266]

Zirpoli H, et al.. Novel approaches for omega-3 fatty acid therapeutics: chronic versus acute administration to protect heart, brain, and spinal cord. Annu Rev. Nutr., 2020, 40: 161-187

[267]

Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet, 2010, 376: 540-550

[268]

Hall JC, Priestley JV, Perry VH, Michael-Titus AT. Docosahexaenoic acid, but not eicosapentaenoic acid, reduces the early inflammatory response following compression spinal cord injury in the rat. J. Neurochem., 2012, 121: 738-750

[269]

Ward RE, Huang W, Curran OE, Priestley JV, Michael-Titus AT. Docosahexaenoic acid prevents white matter damage after spinal cord injury. J. Neurotrauma, 2010, 27: 1769-1780

[270]

Jayedi, A., Soltani, S., Emadi, A., Ghods, K. & Shab-Bidar, S. Dietary intake, biomarkers and supplementation of fatty acids and risk of coronary events: a systematic review and dose-response meta-analysis of randomized controlled trials and prospective observational studies. Critical Rev. Food Sci. Nutrition64, 12363–12382 (2023).

[271]

Engelen M, et al.. ω-3 polyunsaturated fatty acid supplementation improves postabsorptive and prandial protein metabolism in patients with chronic obstructive pulmonary disease: a randomized clinical trial. Am. J. Clin. Nutr., 2022, 116: 686-698

[272]

Jiang H, Galtes D, Wang J, Rockman H. G protein-coupled receptor signaling: transducers and effectors. Am. J. Physiol. Cell Physiol., 2022, 323: C731-C748

[273]

Ghosh T, Chouhan V, Ojha K, Bala K, Bux F. Effects of antibiotic supplementation vs. nutrient stress on α-linolenic acid and α-tocopherol in Scenedesmus sp. Bioresour. Technol., 2025, 418 131968

[274]

Alijani S, Hahn A, Harris WS, Schuchardt JP. Bioavailability of EPA and DHA in humans - a comprehensive review. Prog. Lipid Res., 2025, 97 101318

[275]

Andriambelo B, Stiffel M, Roke K, Plourde M. New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: a scoping review. Ageing Res. Rev., 2023, 85 101835

[276]

Li G, et al.. Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine. Mater. Today Bio, 2024, 28 101181

[277]

Jiang S, et al.. Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis. Gut, 2024, 74: 45-57

[278]

Paredes A, et al.. γ-Linolenic acid in maternal milk drives cardiac metabolic maturation. Nature, 2023, 618: 365-373

[279]

Belayev L, et al.. Neuroprotectin D1 upregulates Iduna expression and provides protection in cellular uncompensated oxidative stress and in experimental ischemic stroke. Cell Death Differ., 2017, 24: 1091-1099

[280]

Ramar, M., Yano, N. & Fedulov, A. V. Intra-airway treatment with synthetic lipoxin A4 and resolvin E2 mitigates neonatal asthma triggered by maternal exposure to environmental particles. Int. J. Mol. Sci.24, 6145 (2023).

[281]

Libreros S, Nshimiyimana R, Lee B, Serhan CN. Infectious neutrophil deployment is regulated by resolvin D4. Blood, 2023, 142: 589-606

[282]

Spite M, et al.. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature, 2009, 461: 1287-1291

[283]

Lee SH, et al.. Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis. Theranostics, 2020, 10: 12111-12126

[284]

Qin Y, et al.. Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function. J. Nanobiotechnol., 2025, 23 106

[285]

Silva RV, et al.. Long-chain omega-3 fatty acids supplementation accelerates nerve regeneration and prevents neuropathic pain behavior in mice. Front. Pharmacol., 2017, 8: 723

[286]

Zhang E, et al.. High omega-3 polyunsaturated fatty acids in fat-1 mice reduce inflammatory pain. J. Med. food, 2017, 20: 535-541

[287]

Kato Y, et al.. Vesicular nucleotide transporter is a molecular target of eicosapentaenoic acid for neuropathic and inflammatory pain treatment. Proc. Natl. Acad. Sci. USA, 2022, 119 e2122158119

[288]

Huang CT, Tsai YJ. Docosahexaenoic acid confers analgesic effects after median nerve injury via inhibition of c-Jun N-terminal kinase activation in microglia. J. Nutr. Biochem., 2016, 29: 97-106

Funding

National Natural Science Foundation of China (National Science Foundation of China)(82220108005)

National Key Research and Development Project of Stem Cell and Transformation Research (2019YFA0112100)

Taishan Scholars Program of Shandong Province-Young Taishan Scholars (tsqn201909197) Cutting Edge Development Fund of Advanced Medical Research Institute (Shandong University)

RIGHTS & PERMISSIONS

The Author(s)

PDF

36

Accesses

0

Citation

Detail

Sections
Recommended

/