Skip to main content

Advertisement

SpringerLink
Log in

Omega-3 fatty acids as regulators of brown/beige adipose tissue: from mechanisms to therapeutic potential

  • Review
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Adipose tissue dysfunction represents the hallmark of obesity. Brown/beige adipose tissues play a crucial role in maintaining energy homeostasis through non-shivering thermogenesis. Brown adipose tissue (BAT) activity has been inversely related to body fatness, suggesting that BAT activation is protective against obesity. BAT plays also a key role in the control of triglyceride clearance, glucose homeostasis, and insulin sensitivity. Therefore, BAT/beige activation has been proposed as a strategy to prevent or ameliorate obesity development and associated commorbidities. In the last few years, a variety of preclinical studies have proposed n-3 polyunsaturated fatty acids (n-3 PUFAs) as novel inducers of BAT activity and white adipose tissue browning. Here, we review the in vitro and in vivo available evidences of the thermogenic properties of n-3 PUFAs, especially focusing on the molecular and cellular physiological mechanisms involved. Finally, we also discuss the challenges and future perspectives to better characterize the therapeutic potential of n-3 PUFAs as browning agents, especially in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Albracht-Schulte K, Kalupahana NS, Ramalingam L, Wang S, Rahman SM, Robert-McComb J, Moustaid-Moussa N (2018) Omega-3 fatty acids in obesity and metabolic syndrome: a mechanistic update. J Nutr Biochem 58:1–16. https://doi.org/10.1016/j.jnutbio.2018.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ansari S, Djalali M, Mohammadzadeh Honarvar N, Mazaherioun M, Zarei M, Agh F, Gholampour Z, Javanbakht MH (2017) The effect of n-3 polyunsaturated fatty acids supplementation on serum Irisin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Int J Endocrinol Metab 15:e40614. https://doi.org/10.5812/ijem.40614

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bargut TC, Silva-e-Silva AC, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB (2016) Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers. Eur J Nutr 55:159–169. https://doi.org/10.1007/s00394-015-0834-0

    Article  CAS  PubMed  Google Scholar 

  4. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmuller A, Gordts PL, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M, Heeren J (2011) Brown adipose tissue activity controls triglyceride clearance. Nat Med 17:200–205. https://doi.org/10.1038/nm.2297

    Article  CAS  PubMed  Google Scholar 

  5. Bartelt A, Heeren J (2014) Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10:24–36. https://doi.org/10.1038/nrendo.2013.204

    Article  CAS  PubMed  Google Scholar 

  6. Bjursell M, Xu X, Admyre T, Bottcher G, Lundin S, Nilsson R, Stone VM, Morgan NG, Lam YY, Storlien LH, Linden D, Smith DM, Bohlooly YM, Oscarsson J (2014) The beneficial effects of n-3 polyunsaturated fatty acids on diet induced obesity and impaired glucose control do not require Gpr120. PLoS One 9:e114942. https://doi.org/10.1371/journal.pone.0114942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:1505S–1519S. https://doi.org/10.1093/ajcn/83.6.1505S

    Article  CAS  PubMed  Google Scholar 

  8. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359. https://doi.org/10.1152/physrev.00015.2003

    Article  CAS  PubMed  Google Scholar 

  9. Blondin DP, Frisch F, Phoenix S, Guerin B, Turcotte EE, Haman F, Richard D, Carpentier AC (2017) Inhibition of intracellular triglyceride lipolysis suppresses cold-induced brown adipose tissue metabolism and increases shivering in humans. Cell Metab 25:438–447. https://doi.org/10.1016/j.cmet.2016.12.005

    Article  CAS  PubMed  Google Scholar 

  10. Catoi AF, Parvu A, Muresan A, Busetto L (2015) Metabolic mechanisms in obesity and type 2 diabetes: insights from bariatric/metabolic surgery. Obes Facts 8:350–363. https://doi.org/10.1159/000441259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cinti S (2017) UCP1 protein: the molecular hub of adipose organ plasticity. Biochimie 134:71–76. https://doi.org/10.1016/j.biochi.2016.09.008

    Article  CAS  PubMed  Google Scholar 

  12. Claria J, Dalli J, Yacoubian S, Gao F, Serhan CN (2012) Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J Immunol 189:2597–2605. https://doi.org/10.4049/jimmunol.1201272

    Article  CAS  PubMed  Google Scholar 

  13. Crescenzo R, Mazzoli A, Cancelliere R, Bianco F, Giacco A, Liverini G, Dulloo AG, Iossa S (2017) Polyunsaturated fatty acids stimulate de novo lipogenesis and improve glucose homeostasis during refeeding with high fat diet. Front Physiol 8:178. https://doi.org/10.3389/fphys.2017.00178

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cypess AM, Haft CR, Laughlin MR, Hu HH (2014) Brown fat in humans: consensus points and experimental guidelines. Cell Metab 20:408–415. https://doi.org/10.1016/j.cmet.2014.07.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, Kolodny GM (2015) Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab 21:33–38. https://doi.org/10.1016/j.cmet.2014.12.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chang SH, Song NJ, Choi JH, Yun UJ, Park KW (2019) Mechanisms underlying UCP1 dependent and independent adipocyte thermogenesis. Obes Rev 20:241–251. https://doi.org/10.1111/obr.12796

    Article  CAS  PubMed  Google Scholar 

  17. Chaurasia B, Kaddai VA, Lancaster GI, Henstridge DC, Sriram S, Galam DL, Gopalan V, Prakash KN, Velan SS, Bulchand S, Tsong TJ, Wang M, Siddique MM, Yuguang G, Sigmundsson K, Mellet NA, Weir JM, Meikle PJ, Bin MYMS, Shabbir A, Shayman JA, Hirabayashi Y, Shiow ST, Sugii S, Summers SA (2016) Adipocyte ceramides regulate subcutaneous adipose browning, inflammation, and metabolism. Cell Metab 24:820–834. https://doi.org/10.1016/j.cmet.2016.10.002

    Article  CAS  PubMed  Google Scholar 

  18. Cholewski M, Tomczykowa M, Tomczyk M (2018) A comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients 10. https://doi.org/10.3390/nu10111662

  19. Dalli J, Serhan CN (2019) Identification and structure elucidation of the pro-resolving mediators provides novel leads for resolution pharmacology. Br J Pharmacol 176:1024–1037. https://doi.org/10.1111/bph.14336

    Article  CAS  PubMed  Google Scholar 

  20. Darcy J, Tseng YH (2019) ComBATing aging-does increased brown adipose tissue activity confer longevity? GeroScience 41:285–296. https://doi.org/10.1007/s11357-019-00076-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Escote X, Felix-Soriano E, Gayoso L, Huerta AE, Alvarado MA, Ansorena D, Astiasaran I, Martinez JA, Moreno-Aliaga MJ (2018) Effects of EPA and lipoic acid supplementation on circulating FGF21 and the fatty acid profile in overweight/obese women following a hypocaloric diet. Food Funct 9:3028–3036. https://doi.org/10.1039/c8fo00355f

    Article  CAS  PubMed  Google Scholar 

  22. Fabbiano S, Suarez-Zamorano N, Rigo D, Veyrat-Durebex C, Stevanovic Dokic A, Colin DJ, Trajkovski M (2016) Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling. Cell Metab 24:434–446. https://doi.org/10.1016/j.cmet.2016.07.023

    Article  CAS  PubMed  Google Scholar 

  23. Fan R, Koehler K, Chung S (2019) Adaptive thermogenesis by dietary n-3 polyunsaturated fatty acids: emerging evidence and mechanisms. Biochim Biophys Acta Mol Cell Biol Lipids 1864:59–70. https://doi.org/10.1016/j.bbalip.2018.04.012

    Article  CAS  PubMed  Google Scholar 

  24. Fan R, Toney AM, Jang Y, Ro SH, Chung S (2018) Maternal n-3 PUFA supplementation promotes fetal brown adipose tissue development through epigenetic modifications in C57BL/6 mice. Biochim Biophys Acta Mol Cell Biol Lipids 1863:1488–1497. https://doi.org/10.1016/j.bbalip.2018.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ferguson JF, Xue C, Hu Y, Li M, Reilly MP (2016) Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans. J Nutr Biochem 30:126–132. https://doi.org/10.1016/j.jnutbio.2015.12.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fleckenstein-Elsen M, Dinnies D, Jelenik T, Roden M, Romacho T, Eckel J (2016) Eicosapentaenoic acid and arachidonic acid differentially regulate adipogenesis, acquisition of a brite phenotype and mitochondrial function in primary human adipocytes. Mol Nutr Food Res 60:2065–2075. https://doi.org/10.1002/mnfr.201500892

    Article  CAS  PubMed  Google Scholar 

  27. Frontini A, Vitali A, Perugini J, Murano I, Romiti C, Ricquier D, Guerrieri M, Cinti S (2013) White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta 1831:950–959. https://doi.org/10.1016/j.bbalip.2013.02.005

    Article  CAS  PubMed  Google Scholar 

  28. Ghandour RA, Colson C, Giroud M, Maurer S, Rekima S, Ailhaud G, Klingenspor M, Amri EZ, Pisani DF (2018) Impact of dietary omega3 polyunsaturated fatty acid supplementation on brown and brite adipocyte function. J Lipid Res 59:452–461. https://doi.org/10.1194/jlr.M081091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Glass CK, Olefsky JM (2012) Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab 15:635–645. https://doi.org/10.1016/j.cmet.2012.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gonzalez-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, Titos E, Martinez-Clemente M, Lopez-Parra M, Arroyo V, Claria J (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J 23:1946–1957. https://doi.org/10.1096/fj.08-125674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Guerra C, Koza RA, Walsh K, Kurtz DM, Wood PA, Kozak LP (1998) Abnormal nonshivering thermogenesis in mice with inherited defects of fatty acid oxidation. J Clin Invest 102:1724–1731. https://doi.org/10.1172/JCI4532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hansen TV, Vik A, Serhan CN (2018) The protectin family of specialized pro-resolving mediators: potent immunoresolvents enabling innovative approaches to target obesity and diabetes. Front Pharmacol 9:1582. https://doi.org/10.3389/fphar.2018.01582

    Article  CAS  PubMed  Google Scholar 

  33. Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252–1263. https://doi.org/10.1038/nm.3361

    Article  CAS  PubMed  Google Scholar 

  34. Heird WC, Lapillonne A (2005) The role of essential fatty acids in development. Annu Rev Nutr 25:549–571. https://doi.org/10.1146/annurev.nutr.24.012003.132254

    Article  CAS  PubMed  Google Scholar 

  35. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91

    Article  CAS  PubMed  Google Scholar 

  36. Huerta AE, Prieto-Hontoria PL, Fernandez-Galilea M, Escote X, Martinez JA, Moreno-Aliaga MJ (2017) Effects of dietary supplementation with EPA and/or alpha-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet. Biofactors 43:117–131. https://doi.org/10.1002/biof.1317

    Article  CAS  PubMed  Google Scholar 

  37. Hwang D, Rhee SH (1999) Receptor-mediated signaling pathways: potential targets of modulation by dietary fatty acids. Am J Clin Nutr 70:545–556. https://doi.org/10.1093/ajcn/70.4.545

    Article  CAS  PubMed  Google Scholar 

  38. Inokuma K, Ogura-Okamatsu Y, Toda C, Kimura K, Yamashita H, Saito M (2005) Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization in brown adipose tissue. Diabetes 54:1385–1391

    Article  CAS  PubMed  Google Scholar 

  39. Itariu BK, Zeyda M, Hochbrugger EE, Neuhofer A, Prager G, Schindler K, Bohdjalian A, Mascher D, Vangala S, Schranz M, Krebs M, Bischof MG, Stulnig TM (2012) Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am J Clin Nutr 96:1137–1149. https://doi.org/10.3945/ajcn.112.037432

    Article  CAS  PubMed  Google Scholar 

  40. Iwen KA, Backhaus J, Cassens M, Waltl M, Hedesan OC, Merkel M, Heeren J, Sina C, Rademacher L, Windjager A, Haug AR, Kiefer FW, Lehnert H, Schmid SM (2017) Cold-induced brown adipose tissue activity alters plasma fatty acids and improves glucose metabolism in men. J Clin Endocrinol Metab 102:4226–4234. https://doi.org/10.1210/jc.2017-01250

    Article  PubMed  Google Scholar 

  41. Kahn CR, Wang G, Lee KY (2019) Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest 129:3990–4000. https://doi.org/10.1172/JCI129187

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kaisanlahti A, Glumoff T (2019) Browning of white fat: agents and implications for beige adipose tissue to type 2 diabetes. J Physiol Biochem 75:1–10. https://doi.org/10.1007/s13105-018-0658-5

    Article  CAS  PubMed  Google Scholar 

  43. Kawabata F, Inoue N, Masamoto Y, Matsumura S, Kimura W, Kadowaki M, Higashi T, Tominaga M, Inoue K, Fushiki T (2009) Non-pungent capsaicin analogs (capsinoids) increase metabolic rate and enhance thermogenesis via gastrointestinal TRPV1 in mice. Biosci Biotechnol Biochem 73:2690–2697. https://doi.org/10.1271/bbb.90555

    Article  CAS  PubMed  Google Scholar 

  44. Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, Vetrivelan R, Lu GZ, Laznik-Bogoslavski D, Hasenfuss SC, Kajimura S, Gygi SP, Spiegelman BM (2015) A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell 163:643–655. https://doi.org/10.1016/j.cell.2015.09.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kim J, Okla M, Erickson A, Carr T, Natarajan SK, Chung S (2016) Eicosapentaenoic acid potentiates brown thermogenesis through FFAR4-dependent up-regulation of miR-30b and miR-378. J Biol Chem 291:20551–20562. https://doi.org/10.1074/jbc.M116.721480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim M, Goto T, Yu R, Uchida K, Tominaga M, Kano Y, Takahashi N, Kawada T (2015) Fish oil intake induces UCP1 upregulation in brown and white adipose tissue via the sympathetic nervous system. Sci Rep 5:18013. https://doi.org/10.1038/srep18013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kwok KH, Lam KS, Xu A (2016) Heterogeneity of white adipose tissue: molecular basis and clinical implications. Exp Mol Med 48:e215. https://doi.org/10.1038/emm.2016.5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ladhani M, Craig JC, Irving M, Clayton PA, Wong G (2017) Obesity and the risk of cardiovascular and all-cause mortality in chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant 32:439–449. https://doi.org/10.1093/ndt/gfw075

    Article  CAS  PubMed  Google Scholar 

  49. Laiglesia LM, Lorente-Cebrian S, Lopez-Yoldi M, Lanas R, Sainz N, Martinez JA, Moreno-Aliaga MJ (2018a) Maresin 1 inhibits TNF-alpha-induced lipolysis and autophagy in 3T3-L1 adipocytes. J Cell Physiol 233:2238–2246. https://doi.org/10.1002/jcp.26096

    Article  CAS  PubMed  Google Scholar 

  50. Laiglesia LM, Lorente-Cebrian S, Martinez-Fernandez L, Sainz N, Prieto-Hontoria PL, Burrell MA, Rodriguez-Ortigosa CM, Martinez JA, Moreno-Aliaga MJ (2018b) Maresin 1 mitigates liver steatosis in ob/ob and diet-induced obese mice. Int J Obes 42:572–579. https://doi.org/10.1038/ijo.2017.226

    Article  CAS  Google Scholar 

  51. Laiglesia LM, Lorente-Cebrian S, Prieto-Hontoria PL, Fernandez-Galilea M, Ribeiro SM, Sainz N, Martinez JA, Moreno-Aliaga MJ (2016) Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects. J Nutr Biochem 37:76–82. https://doi.org/10.1016/j.jnutbio.2016.07.019

    Article  CAS  PubMed  Google Scholar 

  52. Lankinen M, Uusitupa M, Schwab U (2018) Genes and dietary fatty acids in regulation of fatty acid composition of plasma and erythrocyte membranes. Nutrients 10. https://doi.org/10.3390/nu10111785

  53. Lee P, Bova R, Schofield L, Bryant W, Dieckmann W, Slattery A, Govendir MA, Emmett L, Greenfield JR (2016) Brown adipose tissue exhibits a glucose-responsive thermogenic biorhythm in humans. Cell Metab 23:602–609. https://doi.org/10.1016/j.cmet.2016.02.007

    Article  CAS  PubMed  Google Scholar 

  54. Leitner BP, Huang S, Brychta RJ, Duckworth CJ, Baskin AS, McGehee S, Tal I, Dieckmann W, Gupta G, Kolodny GM, Pacak K, Herscovitch P, Cypess AM, Chen KY (2017) Mapping of human brown adipose tissue in lean and obese young men. Proc Natl Acad Sci U S A 114:8649–8654. https://doi.org/10.1073/pnas.1705287114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Liu H, Wang J, He T, Becker S, Zhang G, Li D, Ma X (2018) Butyrate: a double-edged sword for health? Adv Nutr 9:21–29. https://doi.org/10.1093/advances/nmx009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lorente-Cebrian S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ (2009) Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond) 117:243–249. https://doi.org/10.1042/CS20090020

    Article  CAS  Google Scholar 

  57. Lorente-Cebrian S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ (2010) Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. Mol Nutr Food Res 54(Suppl 1):S104–S111. https://doi.org/10.1002/mnfr.200900522

    Article  CAS  PubMed  Google Scholar 

  58. Lorente-Cebrian S, Costa AG, Navas-Carretero S, Zabala M, Laiglesia LM, Martinez JA, Moreno-Aliaga MJ (2015) An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases. J Physiol Biochem 71:341–349. https://doi.org/10.1007/s13105-015-0395-y

    Article  CAS  PubMed  Google Scholar 

  59. Lorente-Cebrian S, Costa AG, Navas-Carretero S, Zabala M, Martinez JA, Moreno-Aliaga MJ (2013) Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence. J Physiol Biochem 69:633–651. https://doi.org/10.1007/s13105-013-0265-4

    Article  CAS  PubMed  Google Scholar 

  60. Ly LD, Xu S, Choi SK, Ha CM, Thoudam T, Cha SK, Wiederkehr A, Wollheim CB, Lee IK, Park KS (2017) Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. Exp Mol Med 49:e291. https://doi.org/10.1038/emm.2016.157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lynes MD, Leiria LO, Lundh M, Bartelt A, Shamsi F, Huang TL, Takahashi H, Hirshman MF, Schlein C, Lee A, Baer LA, May FJ, Gao F, Narain NR, Chen EY, Kiebish MA, Cypess AM, Bluher M, Goodyear LJ, Hotamisligil GS, Stanford KI, Tseng YH (2017) The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med 23:631–637. https://doi.org/10.1038/nm.4297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Martínez-Fernández LF-GM, Félix Soriano E, González-Muniesa P, Moreno-Aliaga MJ (2018) Inflammation and oxidative stress in adipose tissue: nutritional regulation. In: Marti del Moral A, Aguilera CM (eds) Obesity: oxidative stress and dietary antioxidants. Academic Press, Elsevier, London, pp 63–92

    Chapter  Google Scholar 

  63. Martinez-Fernandez L, Gonzalez-Muniesa P, Laiglesia LM, Sainz N, Prieto-Hontoria PL, Escote X, Odriozola L, Corrales FJ, Arbones-Mainar JM, Martinez JA, Moreno-Aliaga MJ (2017) Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet-induced obese mice. FASEB J 31:2135–2145. https://doi.org/10.1096/fj.201600859R

    Article  CAS  PubMed  Google Scholar 

  64. Martinez-Fernandez L, Laiglesia LM, Huerta AE, Martinez JA, Moreno-Aliaga MJ (2015) Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins Other Lipid Mediat 121:24–41. https://doi.org/10.1016/j.prostaglandins.2015.07.003

    Article  CAS  PubMed  Google Scholar 

  65. Matthias A, Ohlson KB, Fredriksson JM, Jacobsson A, Nedergaard J, Cannon B (2000) Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty scid-induced thermogenesis. J Biol Chem 275:25073–25081. https://doi.org/10.1074/jbc.M000547200

    Article  CAS  PubMed  Google Scholar 

  66. Maurer SF, Dieckmann S, Kleigrewe K, Colson C, Amri EZ, Klingenspor M (2019) Fatty acid metabolites as novel regulators of non-shivering thermogenesis. Handb Exp Pharmacol 251:183–214. https://doi.org/10.1007/164_2018_150

    Article  CAS  PubMed  Google Scholar 

  67. Moreno-Aliaga MJ, Lorente-Cebrian S, Martinez JA (2010) Regulation of adipokine secretion by n-3 fatty acids. Proc Nutr Soc 69:324–332. https://doi.org/10.1017/S0029665110001801

    Article  CAS  PubMed  Google Scholar 

  68. Morine MJ, Tierney AC, van Ommen B, Daniel H, Toomey S, Gjelstad IM, Gormley IC, Perez-Martinez P, Drevon CA, Lopez-Miranda J, Roche HM (2011) Transcriptomic coordination in the human metabolic network reveals links between n-3 fat intake, adipose tissue gene expression and metabolic health. PLoS Comput Biol 7:e1002223. https://doi.org/10.1371/journal.pcbi.1002223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Neuhofer A, Zeyda M, Mascher D, Itariu BK, Murano I, Leitner L, Hochbrugger EE, Fraisl P, Cinti S, Serhan CN, Stulnig TM (2013) Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Diabetes 62:1945–1956. https://doi.org/10.2337/db12-0828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384:766–781. https://doi.org/10.1016/S0140-6736(14)60460-8

    Article  PubMed  PubMed Central  Google Scholar 

  71. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, Mukundan L, Brombacher F, Locksley RM, Chawla A (2011) Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104–108. https://doi.org/10.1038/nature10653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, Scott PA, Jenn A, Liu-Bryan R, Glass CK, Neels JG, Olefsky JM (2007) A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 282:35279–35292. https://doi.org/10.1074/jbc.M706762200

    Article  CAS  PubMed  Google Scholar 

  73. Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, Zalevsky J, Dahiyat BI, Chi NW, Olefsky JM (2005) JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem 280:35361–35371. https://doi.org/10.1074/jbc.M504611200

    Article  CAS  PubMed  Google Scholar 

  74. Obesity and overweight (2018). http://www.who.int/mediacentre/factsheets/fs311/en/

  75. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–698. https://doi.org/10.1016/j.cell.2010.07.041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Okla M, Kim J, Koehler K, Chung S (2017) Dietary factors promoting brown and beige fat development and thermogenesis. Adv Nutr 8:473–483. https://doi.org/10.3945/an.116.014332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Okla M, Zaher W, Alfayez M, Chung S (2018) Inhibitory effects of toll-like receptor 4, NLRP3 inflammasome, and interleukin-1beta on white adipocyte browning. Inflammation 41:626–642. https://doi.org/10.1007/s10753-017-0718-y

    Article  CAS  PubMed  Google Scholar 

  78. Oliveira TE, Castro E, Belchior T, Andrade ML, Chaves-Filho AB, Peixoto AS, Moreno MF, Ortiz-Silva M, Moreira RJ, Inague A, Yoshinaga MY, Miyamoto S, Moustaid-Moussa N, Festuccia WT (2019) Fish oil protects wild type and uncoupling protein 1-deficient mice from obesity and glucose intolerance by increasing energy expenditure. Mol Nutr Food Res 63:e1800813. https://doi.org/10.1002/mnfr.201800813

    Article  CAS  PubMed  Google Scholar 

  79. Olmstead KI, La Frano MR, Fahrmann J, Grapov D, Viscarra JA, Newman JW, Fiehn O, Crocker DE, Filipp FV, Ortiz RM (2017) Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. Metabolomics:13. https://doi.org/10.1007/s11306-017-1186-y

  80. Oudart H, Groscolas R, Calgari C, Nibbelink M, Leray C, Le Maho Y, Malan A (1997) Brown fat thermogenesis in rats fed high-fat diets enriched with n-3 polyunsaturated fatty acids. Int J Obes Relat Metab Disord 21:955–962

    Article  CAS  PubMed  Google Scholar 

  81. Pahlavani M, Ramalingam L, Miller EK, Scoggin S, Menikdiwela KR, Kalupahana NS, Festuccia WT, Moustaid-Moussa N (2019) Eicosapentaenoic acid reduces adiposity, glucose intolerance and increases oxygen consumption independently of uncoupling protein 1. Mol Nutr Food Res 63:e1800821. https://doi.org/10.1002/mnfr.201800821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Pahlavani M, Razafimanjato F, Ramalingam L, Kalupahana NS, Moussa H, Scoggin S, Moustaid-Moussa N (2017) Eicosapentaenoic acid regulates brown adipose tissue metabolism in high-fat-fed mice and in clonal brown adipocytes. J Nutr Biochem 39:101–109. https://doi.org/10.1016/j.jnutbio.2016.08.012

    Article  CAS  PubMed  Google Scholar 

  83. Pahlavani M, Wijayatunga NN, Kalupahana NS, Ramalingam L, Gunaratne PH, Coarfa C, Rajapakshe K, Kottapalli P, Moustaid-Moussa N (2018) Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice. Biochim Biophys Acta Mol Cell Biol Lipids 1863:1523–1531. https://doi.org/10.1016/j.bbalip.2018.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Baena MJ, Marti A, Martinez JA, Moreno-Aliaga MJ (2008) Differential inflammatory status in rats susceptible or resistant to diet-induced obesity: effects of EPA ethyl ester treatment. Eur J Nutr 47:380–386. https://doi.org/10.1007/s00394-008-0738-3

    Article  CAS  PubMed  Google Scholar 

  85. Perez-Matute P, Marti A, Martinez JA, Fernandez-Otero MP, Stanhope KL, Havel PJ, Moreno-Aliaga MJ (2005) Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: role of glucose metabolism. Am J Physiol Regul Integr Comp Physiol 288:R1682–R1688. https://doi.org/10.1152/ajpregu.00727.2004

    Article  CAS  PubMed  Google Scholar 

  86. Perez-Matute P, Marti A, Martinez JA, Fernandez-Otero MP, Stanhope KL, Havel PJ, Moreno-Aliaga MJ (2007) Conjugated linoleic acid inhibits glucose metabolism, leptin and adiponectin secretion in primary cultured rat adipocytes. Mol Cell Endocrinol 268:50–58. https://doi.org/10.1016/j.mce.2007.01.013

    Article  CAS  PubMed  Google Scholar 

  87. Pisani DF, Ghandour RA, Beranger GE, Le Faouder P, Chambard JC, Giroud M, Vegiopoulos A, Djedaini M, Bertrand-Michel J, Tauc M, Herzig S, Langin D, Ailhaud G, Duranton C, Amri EZ (2014) The omega6-fatty acid, arachidonic acid, regulates the conversion of white to brite adipocyte through a prostaglandin/calcium mediated pathway. Mol Metab 3:834–847. https://doi.org/10.1016/j.molmet.2014.09.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Prusiner SB, Cannon B, Ching TM, Lindberg O (1968) Oxidative metabolism in cells isolated from brown adipose tissue. 2. Catecholamine regulated respiratory control. Eur J Biochem 7:51–57

    Article  CAS  PubMed  Google Scholar 

  89. Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, Palmiter RD, Chawla A (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:1292–1308. https://doi.org/10.1016/j.cell.2014.03.066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Quesada-Lopez T, Cereijo R, Turatsinze JV, Planavila A, Cairo M, Gavalda-Navarro A, Peyrou M, Moure R, Iglesias R, Giralt M, Eizirik DL, Villarroya F (2016) The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes. Nat Commun 7:13479. https://doi.org/10.1038/ncomms13479

    Article  PubMed  PubMed Central  Google Scholar 

  91. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, Jedrychowski MP, Ruas JL, Wrann CD, Lo JC, Camera DM, Lachey J, Gygi S, Seehra J, Hawley JA, Spiegelman BM (2014) Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 157:1279–1291. https://doi.org/10.1016/j.cell.2014.03.065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Reber J, Willershauser M, Karlas A, Paul-Yuan K, Diot G, Franz D, Fromme T, Ovsepian SV, Beziere N, Dubikovskaya E, Karampinos DC, Holzapfel C, Hauner H, Klingenspor M, Ntziachristos V (2018) Non-invasive measurement of brown fat metabolism based on optoacoustic imaging of hemoglobin gradients. Cell Metab 27:689–701 e684. https://doi.org/10.1016/j.cmet.2018.02.002

    Article  CAS  Google Scholar 

  93. Reed N, Fain JN (1968) Potassium-dependent stimulation of respiration in brown fat cells by fatty acids and lipolytic agents. J Biol Chem 243:6077–6083

    CAS  PubMed  Google Scholar 

  94. Rial E, Poustie A, Nicholls DG (1983) Brown-adipose-tissue mitochondria: the regulation of the 32000-Mr uncoupling protein by fatty acids and purine nucleotides. Eur J Biochem 137:197–203

    Article  CAS  PubMed  Google Scholar 

  95. Rocha DM, Caldas AP, Oliveira LL, Bressan J, Hermsdorff HH (2016) Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis 244:211–215. https://doi.org/10.1016/j.atherosclerosis.2015.11.015

    Article  CAS  PubMed  Google Scholar 

  96. Saely CH, Geiger K, Drexel H (2012) Brown versus white adipose tissue: a mini-review. Gerontology 58:15–23. https://doi.org/10.1159/000321319

    Article  PubMed  Google Scholar 

  97. Sceneay J, McAllister SS (2017) The skinny on obesity and cancer. Nat Cell Biol 19:887–888. https://doi.org/10.1038/ncb3583

    Article  CAS  PubMed  Google Scholar 

  98. Smith U, Kahn BB (2016) Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J Intern Med 280:465–475. https://doi.org/10.1111/joim.12540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sun L, Xie H, Mori MA, Alexander R, Yuan B, Hattangadi SM, Liu Q, Kahn CR, Lodish HF (2011) Mir193b-365 is essential for brown fat differentiation. Nat Cell Biol 13:958–965. https://doi.org/10.1038/ncb2286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Svensson PA, Lindberg K, Hoffmann JM, Taube M, Pereira MJ, Mohsen-Kanson T, Hafner AL, Rizell M, Palming J, Dani C, Svensson MK (2014) Characterization of brown adipose tissue in the human perirenal depot. Obesity (Silver Spring) 22:1830–1837. https://doi.org/10.1002/oby.20765

    Article  CAS  Google Scholar 

  101. Takahashi Y, Ide T (2000) Dietary n-3 fatty acids affect mRNA level of brown adipose tissue uncoupling protein 1, and white adipose tissue leptin and glucose transporter 4 in the rat. Br J Nutr 84:175–184

    Article  CAS  PubMed  Google Scholar 

  102. Taraghijou P, Safaeiyan A, Mobasseri M, Ostadrahimi A (2012) The effect of n-3 long chain fatty acids supplementation on plasma peroxisome proliferator activated receptor gamma and thyroid hormones in obesity. J Res Med Sci 17:942–946

    PubMed  PubMed Central  Google Scholar 

  103. Thaker VV (2017) Genetic and epigenetic causes of obesity. Adolesc Med State Art Rev 28:379–405

    PubMed  PubMed Central  Google Scholar 

  104. Titos E, Claria J (2013) Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation. Prostaglandins Other Lipid Mediat 107:77–84. https://doi.org/10.1016/j.prostaglandins.2013.05.003

    Article  CAS  PubMed  Google Scholar 

  105. Titos E, Rius B, Gonzalez-Periz A, Lopez-Vicario C, Moran-Salvador E, Martinez-Clemente M, Arroyo V, Claria J (2011) Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol 187:5408–5418. https://doi.org/10.4049/jimmunol.1100225

    Article  CAS  PubMed  Google Scholar 

  106. Titos E, Rius B, Lopez-Vicario C, Alcaraz-Quiles J, Garcia-Alonso V, Lopategi A, Dalli J, Lozano JJ, Arroyo V, Delgado S, Serhan CN, Claria J (2016) Signaling and immunoresolving actions of resolvin D1 in inflamed human visceral adipose tissue. J Immunol 197:3360–3370. https://doi.org/10.4049/jimmunol.1502522

    Article  CAS  PubMed  Google Scholar 

  107. Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C (2018) Obesity as a disease. Med Clin North Am 102:13–33. https://doi.org/10.1016/j.mcna.2017.08.004

    Article  PubMed  Google Scholar 

  108. Vernochet C, Mourier A, Bezy O, Macotela Y, Boucher J, Rardin MJ, An D, Lee KY, Ilkayeva OR, Zingaretti CM, Emanuelli B, Smyth G, Cinti S, Newgard CB, Gibson BW, Larsson NG, Kahn CR (2012) Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metab 16:765–776. https://doi.org/10.1016/j.cmet.2012.10.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Villarroya F, Cereijo R, Gavalda-Navarro A, Villarroya J, Giralt M (2018a) Inflammation of brown/beige adipose tissues in obesity and metabolic disease. J Intern Med 284:492–504. https://doi.org/10.1111/joim.12803

    Article  CAS  PubMed  Google Scholar 

  110. Villarroya F, Cereijo R, Villarroya J, Gavalda-Navarro A, Giralt M (2018b) Toward an understanding of how immune cells control brown and beige adipobiology. Cell Metab 27:954–961. https://doi.org/10.1016/j.cmet.2018.04.006

    Article  CAS  PubMed  Google Scholar 

  111. Villarroya F, Cereijo R, Villarroya J, Giralt M (2017a) Brown adipose tissue as a secretory organ. Nat Rev Endocrinol 13:26–35. https://doi.org/10.1038/nrendo.2016.136

    Article  CAS  PubMed  Google Scholar 

  112. Villarroya F, Gavalda-Navarro A, Peyrou M, Villarroya J, Giralt M (2017b) The lives and times of brown adipokines. Trends Endocrinol Metab 28:855–867. https://doi.org/10.1016/j.tem.2017.10.005

    Article  CAS  PubMed  Google Scholar 

  113. Villarroya F, Gavalda-Navarro A, Peyrou M, Villarroya J, Giralt M (2019) Brown adipokines. Handb Exp Pharmacol 251:239–256. https://doi.org/10.1007/164_2018_119

    Article  CAS  PubMed  Google Scholar 

  114. Villarroya F, Vidal-Puig A (2013) Beyond the sympathetic tone: the new brown fat activators. Cell Metab 17:638–643. https://doi.org/10.1016/j.cmet.2013.02.020

    Article  CAS  PubMed  Google Scholar 

  115. Villarroya J, Flachs P, Redondo-Angulo I, Giralt M, Medrikova D, Villarroya F, Kopecky J, Planavila A (2014) Fibroblast growth factor-21 and the beneficial effects of long-chain n-3 polyunsaturated fatty acids. Lipids 49:1081–1089. https://doi.org/10.1007/s11745-014-3948-x

    Article  CAS  PubMed  Google Scholar 

  116. Vinci L, Krieger JP, Braun J, Pestoni G, Bender N, Rohrmann S, Faeh D, Staub K (2019) Clustering of sociodemographic and lifestyle factors among adults with excess weight in a multilingual country. Nutrition 62:177–185. https://doi.org/10.1016/j.nut.2019.01.001

    Article  PubMed  Google Scholar 

  117. Wang L, Chen L, Liu Z, Liu Y, Luo M, Chen N, Deng X, Luo Y, He J, Zhang L, Hill MA, Li R, Wu J (2018) PAI-1 exacerbates white adipose tissue dysfunction and metabolic dysregulation in high fat diet-induced obesity. Front Pharmacol 9:1087. https://doi.org/10.3389/fphar.2018.01087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Wang TY, Liu M, Portincasa P, Wang DQ (2013) New insights into the molecular mechanism of intestinal fatty acid absorption. Eur J Clin Investig 43:1203–1223. https://doi.org/10.1111/eci.12161

    Article  CAS  Google Scholar 

  119. Wang YL, Lin SP, Hsieh PC, Hung SC (2016) Concomitant beige adipocyte differentiation upon induction of mesenchymal stem cells into brown adipocytes. Biochem Biophys Res Commun 478:689–695. https://doi.org/10.1016/j.bbrc.2016.08.008

    Article  CAS  PubMed  Google Scholar 

  120. Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, Laboy R, Hirschey MD, Mair WB (2017) Dietary restriction and AMPK increase lifespan via mitochondrial network and peroxisome remodeling. Cell Metab 26:884–896 e885. https://doi.org/10.1016/j.cmet.2017.09.024

    Article  CAS  Google Scholar 

  121. Woo CY, Jang JE, Lee SE, Koh EH, Lee KU (2019) Mitochondrial dysfunction in adipocytes as a primary cause of adipose tissue inflammation. Diabetes Metab J. https://doi.org/10.4093/dmj.2018.0221

  122. Worsch S, Heikenwalder M, Hauner H, Bader BL (2018) Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating metabolic pathways conveying anti-obesogenic effects in mice. Nutr Metab (Lond) 15:65. https://doi.org/10.1186/s12986-018-0291-x

    Article  CAS  Google Scholar 

  123. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376. https://doi.org/10.1016/j.cell.2012.05.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Yu R, Park JS, Kawada T, Kwon BS (2002) Alteration of a macrophages inflammatory protein-related protein-2 (MRP-2) response by high fat and cholesterol diet in mice. Life Sci 70:2535–2545

    Article  CAS  PubMed  Google Scholar 

  125. Yu Y, Cai J, She Z, Li H (2019) Insights into the epidemiology, pathogenesis, and therapeutics of nonalcoholic fatty liver diseases. Adv Sci (Weinh) 6:1801585. https://doi.org/10.1002/advs.201801585

    Article  CAS  Google Scholar 

  126. Zhang D, Xie T, Leung PS (2018) Irisin ameliorates glucolipotoxicity-associated beta-cell dysfunction and apoptosis via AMPK signaling and anti-inflammatory actions. Cell Physiol Biochem 51:924–937. https://doi.org/10.1159/000495395

    Article  CAS  PubMed  Google Scholar 

  127. Zhao M, Chen X (2014) Eicosapentaenoic acid promotes thermogenic and fatty acid storage capacity in mouse subcutaneous adipocytes. Biochem Biophys Res Commun 450:1446–1451. https://doi.org/10.1016/j.bbrc.2014.07.010

    Article  CAS  PubMed  Google Scholar 

  128. Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, Nedergaard J, Cinti S (2009) The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J 23:3113–3120. https://doi.org/10.1096/fj.09-133546

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was funded by Ministry of Economy, Industry and Competitiveness (MINECO-FEDER) of the Government of Spain (BFU2015-65937-R), Department of Health of the Navarra Government (67-2015), and CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Carlos III Health Research Institute (CB12/03/30002). “Juan de la Cierva” Grant to M.F.-G. (IJCI-2016-30025). This research also received support from Centre for Nutrition Research of the University of Navarra.

Author information

Author notes

  1. Xavier Escoté

    Present address: Unitat de Nutrició i Salut, Centre Tecnològic de Catalunya, Eurecat, Reus, Spain

Authors and Affiliations

  1. University of Navarra, Centre for Nutrition Research and Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Pamplona, Spain

    Marta Fernández-Galilea, Elisa Félix-Soriano, Ignacio Colón-Mesa, Xavier Escoté & Maria J. Moreno-Aliaga

  2. IDISNA, Navarra’s Health Research Institute, Pamplona, Spain

    Marta Fernández-Galilea & Maria J. Moreno-Aliaga

  3. CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain

    Maria J. Moreno-Aliaga

Authors
  1. Marta Fernández-Galilea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisa Félix-Soriano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ignacio Colón-Mesa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xavier Escoté
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria J. Moreno-Aliaga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria J. Moreno-Aliaga.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Key points

• n-3 PUFAs are regulators of the thermogenic program in brown/beige adipocytes.

• n-3 PUFA thermogenic actions involve UCP1-dependent and UCP1-independent mechanisms.

• n-3 PUFAs regulate fetal BAT and offspring metabolism via epigenetic modifications.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernández-Galilea, M., Félix-Soriano, E., Colón-Mesa, I. et al. Omega-3 fatty acids as regulators of brown/beige adipose tissue: from mechanisms to therapeutic potential. J Physiol Biochem 76, 251–267 (2020). https://doi.org/10.1007/s13105-019-00720-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-019-00720-5

Keywords

Search

Navigation