Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management

Abstract

An increase in adiposity is associated with altered levels of biologically active proteins. These include the hormones adiponectin and leptin. The marked change in circulating concentrations of these hormones in obesity has been associated with the development of insulin resistance and metabolic syndrome. Variations in dietary lipid consumption have also been shown to impact obesity. Specifically, omega-3 fatty acids have been correlated with the prevention of obesity and subsequent development of chronic disease sequalae. This review explores animal and human data relating to the effects of omega-3 fatty acids (marine lipids) on adiponectin and leptin, considering plausible mechanisms and potential implications for obesity management. Current evidence suggests a positive, dose-dependent relationship between omega-3 fatty acid intake and circulating levels of adiponectin. In obese subjects, this may translate into a reduced risk of developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese subjects, omega-3 is observed to decrease circulating levels of leptin; however, omega-3-associated increases in leptin levels have been observed in obese subjects. This may pose benefits in the prevention of weight regain in these subjects following calorie restriction.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K . Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006; 116: 1784–1792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang F, Basinski M, Beals J, Briggs S, Churgay L, Clawson D et al. Human obesity protein, leptin. RCSB Protein Data Bank. Nature 1997; 387: 206–209.

    Article  CAS  PubMed  Google Scholar 

  3. Krauss R, Eckel R, Howard B, Appel L, Daniels S, Deckelbaum R et al. AHA Dietary Guidelines Revision 2000: a statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation 2000; 102: 2284–2299.

    Article  CAS  PubMed  Google Scholar 

  4. Meier U, Gressner A . Endocrine Regulation of Energy Metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin and resistin. Clin Chem 2004; 50: 1511–1525.

    Article  CAS  PubMed  Google Scholar 

  5. Knudson J, Dick G, Tune J . Adipokines and coronary vasomotor dysfunction. Exp Biol Med 2007; 232: 727–736.

    CAS  Google Scholar 

  6. Cavusoglu E, Ruwende C, Chopra V, Yanamadala S, Eng C, Clark LT et al. Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain. Eur Heart J 2006; 27: 2300–2309.

    Article  CAS  PubMed  Google Scholar 

  7. Kaidar-Person O, Person B, Szomstein S, Rosenthal R . Nutritional deficiencies in morbidly obese patients: a new form of malnutrition? Part A: Vitamins. Obes Surg 2008; 18: 870–876.

    Article  PubMed  Google Scholar 

  8. Ren J . Leptin and hyperleptinemia—from friend to foe for cardiovascular function. J Endocrinol 2004; 181: 1–10.

    Article  CAS  PubMed  Google Scholar 

  9. Sattar N, Wannamethee G, Sarwar N, Tchernova J, Cherry L, Wallace A et al. Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 2006; 114: 623–629.

    Article  CAS  PubMed  Google Scholar 

  10. Civitarese A, Ukropcova B, Carling S, Hulver M, DeFronzo R, Mandarino L et al. Role of adiponectin in human skeletal muscle bioenergetics. Cell Metab 2006; 4: 75–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002; 8: 731–737.

    Article  CAS  PubMed  Google Scholar 

  12. Dekker J, Funahashi T, Nijpels G, Pilz S, Stehouwer C, Snijder M et al. Prognostic value of adiponectin for cardiovascular disease and mortality. J Clin Endocrinol Metab 2008; 93: 1489–1496.

    Article  CAS  PubMed  Google Scholar 

  13. Nakamura Y, Shimada K, Fukuda D, Shimada Y, Ehara S, Hirose M et al. Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart 2004; 90: 528–533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB . Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291: 1730–1737.

    Article  CAS  PubMed  Google Scholar 

  15. Considine R, Sinha V, Heiman M, Kriauciunas A, Stephens T, Nyce M et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–295.

    Article  CAS  PubMed  Google Scholar 

  16. Frederich R, Hamann A, Anderson S, Lollmann V, Lowell B, Flier J . Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1995; 1: 1311–1314.

    Article  CAS  PubMed  Google Scholar 

  17. Skurk T, Alberti-Huber C, Herder C, Hauner H . Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92: 1023–1033.

    Article  CAS  PubMed  Google Scholar 

  18. Houseknecht K, Baile C, Matteri R, Spurlock M . The biology of leptin: a review. J Anim Sci 1998; 76: 1405–1420.

    Article  CAS  PubMed  Google Scholar 

  19. Auwerx J, Staels B . Leptin. Lancet 1998; 351: 737–742.

    Article  CAS  PubMed  Google Scholar 

  20. Jequier E . Leptin signaling, adiposity, and energy balance. Ann NY Acad Sci 2002; 967: 379–388.

    Article  CAS  PubMed  Google Scholar 

  21. Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL . Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 1997; 82: 561–565.

    CAS  PubMed  Google Scholar 

  22. Cameron AJ, Welborn TA, Zimmet PZ, Dunstan DW, Owen N, Salmon J et al. Overweight and obesity in Australia: the 1999–2000 Australian Diabetes, Obesity and Lifestyle Study (AusDiab). MJA 2003; 178: 427–432.

    PubMed  Google Scholar 

  23. Madsen E, Bruun J, Skogstrand K, Hougaard D, Christiansen T, Richelsen B . Long-term weight loss decreases the nontraditional cardiovascular risk factors interleukin-18 and matrix metalloproteinase-9 in obese subjects. Metabolism 2009; 58: 946–953.

    Article  CAS  PubMed  Google Scholar 

  24. Jequier E . Obesity. Impairment of energy intake or of energy expenditure. Ann Endocrinol (Paris) 1995; 56: 87–92.

    CAS  Google Scholar 

  25. Legradi G, Emerson CH, Ahima RS, Flier JS, Lechan RM . Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 1997; 138: 2569–2576.

    Article  CAS  PubMed  Google Scholar 

  26. Friedman J, Halass J . Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–777.

    Article  CAS  PubMed  Google Scholar 

  27. Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ et al. Leptin regulates proinflammatory immune responses. FASEB J 1998; 12: 57–65.

    Article  CAS  PubMed  Google Scholar 

  28. Shamsuzzaman AS, Winnicki M, Wolk R, Svatikova A, Phillips BG, Davison DE et al. Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 2004; 109: 2181–2185.

    Article  CAS  PubMed  Google Scholar 

  29. Corsonello A, Perticone F, Malara A, De Domenico D, Loddo S, Buemi M et al. Leptin-dependent platelet aggregation in healthy, overweight and obese subjects. Int J Obes Relat Metab Disord 2003; 27: 566–573.

    Article  CAS  PubMed  Google Scholar 

  30. Konstantinides S, Schafer K, Loskutoff DJ . The prothrombotic effects of leptin possible implications for the risk of cardiovascular disease in obesity. Ann NY Acad Sci 2001; 947: 134–141. discussion 41–2.

    Article  CAS  PubMed  Google Scholar 

  31. Rolls B, Drewnowski A, Ledikwe J . Changing the energy density of the diet as a strategy for weight management. J Am Diet Assoc 2005; 105: S98–S103.

    Article  PubMed  Google Scholar 

  32. Moussavi N, Gavino V, Receveur O . Could the quality of dietary fat, and not just its quantity, be related to risk of obesity? Obesity 2008; 16: 7–15.

    Article  PubMed  Google Scholar 

  33. Duncan K, Bacon I, Weinsier R . The effects of high and low energy density diets on satiety, energy intake, and eating time of obese and nonobese subjects. Am J Clin Nutr 1983; 37: 763–767.

    Article  CAS  PubMed  Google Scholar 

  34. Johansson L, Solvoll K, Bjorneboe G, Drevon C . Under- and overreporting of energy intake related to weight status and lifestyle in a nationwide sample. Am J Clin Nutr 1998; 68: 266–274.

    Article  CAS  PubMed  Google Scholar 

  35. Micallef M, Munro I, Phang M, Garg M . Plasma n-3 polyunsaturated fatty acids are negatively associated with obesity. Brit J Nutr 2009; 102: 1370–1374.

    Article  CAS  PubMed  Google Scholar 

  36. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar M, Hensler M et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 2006; 49: 394–397.

    Article  CAS  PubMed  Google Scholar 

  37. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Am Heart Assoc J 2007; 27: 1918–1925.

    CAS  Google Scholar 

  38. Marchioli R, Valagussa F . The results of the GISSI-Prevenzione trial in the general framework of secondary prevention. Eur Heart J 2000; 21: 949–952.

    Article  CAS  PubMed  Google Scholar 

  39. Ruxton C, Reed S, Simpson M, Millington K . The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Diet 2004; 17: 449–459.

    Article  CAS  PubMed  Google Scholar 

  40. Mozaffarian D, Rimm EB . Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006; 296: 1885–1899.

    Article  CAS  PubMed  Google Scholar 

  41. Wang Z, Al-Regaiey KA, Masternak MM, Bartke A . Adipocytokines and lipid levels in Ames dwarf and calorie-restricted mice. J Ferontol Ser A Biol Sci Med Sci 2006; 61A: 323–331.

    CAS  Google Scholar 

  42. Nahin R, Barnes P, Stussman B, Bloom B . Costs of Complementary and Alternative Medicine (CAM) and Frequency of Visits to CAM Practitioners: United States, 2007. US Department of Health and Human Services, Centers for Disease Control and Prevention: Hyattsville, USA, 2009.

    Google Scholar 

  43. National Institutes of Health. Get the Facts: Omega-3 Supplements: An Introduction. Department of Health and Human Services: Bethesda, MD, USA, 2012.

  44. Mori T, Bao D, Burke V, Puddey I, Watts G, Beilin L . Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. Am J Clin Nutr 1999; 70: 817–825.

    Article  CAS  PubMed  Google Scholar 

  45. Simopoulos A . Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999; 70 (suppl), S560–S569.

    Article  Google Scholar 

  46. Simopoulos A . Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002; 21: 495–505.

    Article  CAS  PubMed  Google Scholar 

  47. Serhan C, Arita M, Hong S, Gotlinger K . Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirintriggered epimers. Lipids 2004; 39: 1125–1132.

    Article  CAS  PubMed  Google Scholar 

  48. Babcock T, Kurland A, Helton W, Rahman A, Anwar K, Espat N . Inhibition of activator protein-1 transcription factor activation by omega-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases. Parenter Enteral Nutr 2003; 27: 176–180.

    Article  CAS  Google Scholar 

  49. Ren B, Thelen A, Peters J, Gonzalez F, Jump D . Polyunsaturated fatty acid suppression of hepatic fatty acid. Synthase and S14 gene expression does not require peroxisome proliferator-activated receptor alpha. J Biol Chem 1997; 272: 26827–26832.

    Article  CAS  PubMed  Google Scholar 

  50. Harris W, Miller M, Tighe A, Davidson M, Schaefer E . Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 2008; 197: 12–24.

    Article  CAS  PubMed  Google Scholar 

  51. Morris M, Sacks F, Rosnerm B . Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 1993; 88: 523–533.

    Article  CAS  PubMed  Google Scholar 

  52. Appel L, Miller E, Seidler A, Whelton P . Does supplementation of diet with ‘fish oil’ reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med 1993; 153: 1429–1438.

    Article  CAS  PubMed  Google Scholar 

  53. Harris W . n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997; 65: 1645–54S.

    Article  Google Scholar 

  54. Hansson G . Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005; 352: 1685–1695.

    Article  CAS  PubMed  Google Scholar 

  55. Hotamisligil G, Arner P, Caro J, Atkinson R, Spiegelman B . Increased adipose tissue expression of tumor necrosis factor-a in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409–2415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kressel G, Trunz B, Bub A, Hülsmann O, Wolters M, Lichtinghagen R et al. Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk. Atherosclerosis 2009; 202: 263–271.

    Article  CAS  PubMed  Google Scholar 

  57. Heart Foundation Australia. Fish, fish oils, n-3 polyunsaturated fatty acids and cardiovascular health. Heart Foundation Australia 2008, [cited 25 May 2010]; Available from http://www.heartfoundation.org.au/SiteCollectionDocuments/HW_FS_FishOils_PS_FINAL_web.pdf.

  58. Rizos E, Ntzani E, Bika E, Kostapanos M, Elisaf M . Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 2012; 308: 1024–1033.

    Article  CAS  PubMed  Google Scholar 

  59. Holub B . Clinical nutrition: omega-3 fatty acids in cardiovascular care. CMAJ 2002; 166: 608–615.

    PubMed  PubMed Central  Google Scholar 

  60. Jorgensen M, Bjeregaard P, Borch- Johnsen K . Diabetes and impaired glucose tolerance among the Inuit population of Greenland. Diabetes Care 2002; 25: 1766–1771.

    Article  PubMed  Google Scholar 

  61. Mouratoff G, Scott E . Diabetes mellitus in Eskimos after a decade. JAMA 1973; 226: 1345–1346.

    Article  CAS  PubMed  Google Scholar 

  62. Young T, Schraer C, Shubnikoff E, Szathmary E, Nikitin Y . Prevalence of diagnosed diabetes in circumpolar indigenous populations. Int J Epidemiol 1992; 21: 730–736.

    Article  CAS  PubMed  Google Scholar 

  63. Burrows N, Geiss L, Engelgau M, Acton K . Prevalence of diabetes among Native Americans and Alaska Natives, 1990–1997: an increasing burden. Diabetes Care 2000; 23: 1786–1790.

    Article  CAS  PubMed  Google Scholar 

  64. Simonsen T, Vartun A, Lyngmo V, Nordoy A . Coronary heart disease, serum lipids, platelets and dietary fish in two communities in northern Norway. Acta Med Scand 1987; 222: 237–245.

    Article  CAS  PubMed  Google Scholar 

  65. Adler A, Boyko E, Schraer C, Murphy N . Lower prevalence of impaired glucose tolerance and diabetes associated with daily seal oil or salmon consumption among Alaska Natives. Diab Care 1994; 17: 1498–1501.

    Article  CAS  Google Scholar 

  66. Feskens E, Virtanen S, Rasanen L, Tuomilehto J, Stengard J, Pekkanen J et al. Dietary factors determining diabetes and impaired glucose tolerance: a 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study. Diab Care 1995; 18: 1104–1112.

    Article  CAS  Google Scholar 

  67. Hartweg J, Perera R, Montori V, Dinneen S, Neil A, Farmer A . Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus (Review). Cochrane Database Syst Rev 2008; 1: 1–60.

    Google Scholar 

  68. Neschen S, Morino K, Rossbacher J, Pongratz R, Cline G, Sono S et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 2006; 55: 924–928.

    Article  CAS  PubMed  Google Scholar 

  69. Pérez-Matute P, Pérez-Echarri N, Martínez J, Marti A, Moreno-Aliaga M . Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α. Br J Nutr 2007; 97: 389–398.

    Article  CAS  PubMed  Google Scholar 

  70. Rossi AS, Lombardo YB, Lacorte JM, Chicco AG, Rouault C, Slama G et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol 2005; 289: R486–R494.

    Article  CAS  PubMed  Google Scholar 

  71. Burghardt P, Kemmerer E, Buck B, Osetek A, Yan C, Koch L et al. Dietary n-3:n-6 fatty acid ratios differentially influence hormonal signature in a rodent model of metabolic syndrome relative to healthy controls. Nutr Metab 2010; 7: 1–6.

    Article  CAS  Google Scholar 

  72. Buettner R, Scholmerich J, Bollheimer L . High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity 2007; 15: 798–808.

    Article  CAS  PubMed  Google Scholar 

  73. Kondo K, Morino K, Nishio Y, Kondo M, Fuke T, Ugi S et al. Effects of a fish-based diet on the serum adiponectin concentration in young, non-obese, healthy Japanese subjects. J Atheroscler Thromb 2010; 17: 628–637.

    Article  CAS  PubMed  Google Scholar 

  74. Nomura S, Shouzu A, Omoto S, Inami N, Ueba T, Urase F et al. Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes. J Atheroscler Thromb 2009; 16: 83–90.

    Article  CAS  PubMed  Google Scholar 

  75. Gammelmark A, Madsen T, Varming K, Lundbye-Christensen S, Schmidt E . Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects. Nutr Res 2012; 32: 15–23.

    Article  CAS  PubMed  Google Scholar 

  76. Patel JV, Lee KW, Tomson J, Dubb K, Hughes EA, Lip GY . Effects of omega-3 polyunsaturated fatty acids on metabolically active hormones in patients post-myocardial infarction. Int J Cardiol 2007; 115: 42–45.

    Article  PubMed  Google Scholar 

  77. Murata M, Kaji H, Takahashi Y, Iida K, Mizuno I, Okimura Y et al. Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro. Biochem Biophys Res Commun 2000; 270: 343–348.

    Article  CAS  PubMed  Google Scholar 

  78. Perez-Matute P, Marti A, Martinez JA, Fernandez-Otero MP, Stanhope KL, Havel PJ et al. Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: Role of glucose metabolism. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1682–R1688.

    Article  CAS  PubMed  Google Scholar 

  79. Mori TA, Burke V, Puddey IB, Shaw JE, Beilin LJ . Effect of fish diets and weight loss on serum leptin concentration in overweight, treated-hypertensive subjects. J Hypertens 2004; 22: 1983–1990.

    Article  CAS  PubMed  Google Scholar 

  80. Winnicki M, Somers VK, Accurso V, Phillips BG, Puato M, Palatini P et al. Fish-rich diet, leptin, and body mass. Circulation 2002; 106: 289–291.

    Article  CAS  PubMed  Google Scholar 

  81. Peyron-Caso E, Taverna M, Guerre-Millo Ml, se AVr, Pacher N, Slama Gr et al. Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats. J Nutr 2002; 132: 2235–2240.

    Article  CAS  PubMed  Google Scholar 

  82. Rosicka M, Krsek M, Matoulek M, Jarkovska Z, Marek J, Justova V et al. Serum ghrelin levels in obese patients: the relationship to serum leptin levels and soluble leptin receptors levels. Physiol Res 2003; 52: 61–66.

    CAS  PubMed  Google Scholar 

  83. Greenberg JA, Boozer CN . The leptin-fat ratio is constant, and leptin may be part of two feedback mechanisms for maintaining the body fat set point in non-obese male Fischer 344 rats. Horm Metab Res 1999; 31: 525–532.

    Article  CAS  PubMed  Google Scholar 

  84. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005; 115: 3579–3586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ahima R, Kelly J, Elmquist J, Flier J . Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia. Endocrinology 1999; 140: 4923–4931.

    Article  CAS  PubMed  Google Scholar 

  86. Itariu B, Zeyda M, Hochbrugger E, Neuhofer A, Prager G, Schindler K et al. Long-chain n−3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am J Clin Nutr 2012; 96: 1137–1149.

    Article  CAS  PubMed  Google Scholar 

  87. Koh K, Quon M, Shin K, Lim S, Lee Y, Sakuma I et al. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis 2012; 220: 537–544.

    Article  CAS  PubMed  Google Scholar 

  88. Neale E, Muhlhausler B, Probst Y, Batterham M, Fernandez F, Tapsell L . Short-term effects of fish and fish oil consumption on total and high molecular weight adiponectin levels in overweight and obese adults. Metabolism 2013; 62: 651–660.

    Article  CAS  PubMed  Google Scholar 

  89. Yannakoulia M, Yiannakouris N, Blüher S, Matalas A, Klimis-Zacas D, Mantzoros C . Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrino Metab 2003; 88: 1730–1736.

    Article  CAS  Google Scholar 

  90. Yu Y, Zhu H . Chronological changes in metabolism and functions of cultured adipocytes: a hypothesis for cell aging in mature adipocytes. Am J Physiol Endocrinol Metab 2004; 286: E402–E410.

    Article  CAS  PubMed  Google Scholar 

  91. Koh E, Park J, Park H, Jeon M, Ryu J, Kim M et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes 2007; 56: 2973–2981.

    Article  CAS  PubMed  Google Scholar 

  92. Choo H, Kim J, Kwon O, Lee C, Mun J, Han S et al. Mitochondria are impaired in the adipocytes of type 2 diabetic mice. Diabetologia 2006; 49: 784–791.

    Article  CAS  PubMed  Google Scholar 

  93. Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K et al. The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 2001; 276: 41245–41254.

    Article  CAS  PubMed  Google Scholar 

  94. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K et al. PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 2001; 50: 2094–2099.

    Article  CAS  PubMed  Google Scholar 

  95. Karbowska J, Kochan Z . Effect of DHEA on endocrine functions of adipose tissue, the involvement of PPARg. Biochem Pharmacol 2005; 70: 249–257.

    Article  CAS  PubMed  Google Scholar 

  96. van Vonderen M, van Agtmael M, Hassink E, Milinkovic A, Brinkman K, Geerlings S et al. Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss. PLoS One 2009; 4: e5647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Addy C, Gavrila A, Tsiodras S, Brodovicz K, Karchmer A, Mantzoros C . Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrino Metab 2003; 88: 627–636.

    Article  CAS  Google Scholar 

  98. Ferranti Sd, Mozaffarian D . The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem 2008; 54: 945–955.

    Article  CAS  PubMed  Google Scholar 

  99. Pot G, Brouwer I, Enneman A, Rijkers G, Kampman E, Geelen A . No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-aged individuals. Eu J Clin Nutr 2009; 63: 1353–1359.

    Article  CAS  Google Scholar 

  100. Lo C-J, Chiu KC, Fu M, Lo R, Helton S . Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NFkB activity. J Surg Res 1999; 82: 216–221.

    Article  CAS  PubMed  Google Scholar 

  101. Ohata T, Fukuda K, Takahashi M, Sugimura T, Wakabayashi K . Suppression of nitric oxide production in lipopolysaccharide-stimulated macrophage cells by omega 3 polyunsaturated fatty acids. Jpn J Cancer Res 1997; 88: 234–237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Khair-El-Din T, Sicher S, Vazquez M, Chung G, Stallworth K, Kitamura K et al. Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils. J Exp Med 1996; 183: 1241–1246.

    Article  CAS  PubMed  Google Scholar 

  103. Endres S, Ghorbani R, Kelley V, Georgilis K, Lonnemann G, van der Meer J et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989; 320: 265–271.

    Article  CAS  PubMed  Google Scholar 

  104. Kremer J, Lawrence D, Jubiz W, Di Giacomo R, Rynes R, Bartholomew L et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. clinical and immunological effects. Arthritis Rheum 1990; 33: 810–820.

    Article  CAS  PubMed  Google Scholar 

  105. Khalfoun B, Thibault F, Watier H, Bardos P, Lebranchu Y . Docosahexaenoic and eisosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. Adv Exp Med Biol 1997; 400B: 589–597.

    CAS  PubMed  Google Scholar 

  106. Endres S . n-3 Polyunsaturated fatty acids and human cytokine synthesis. Lipids 1996; 31: S239–S242.

    Article  CAS  PubMed  Google Scholar 

  107. Meydani S, Endres S, Woods M, Goldin B, Soo C, Morrill L et al. Oral n-3 fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison in young and older women. J Nutr 1991; 121: 547–555.

    Article  CAS  PubMed  Google Scholar 

  108. Yudkin J, Stehouwer C, Emeis J, Coppack S . C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19: 972–978.

    Article  CAS  PubMed  Google Scholar 

  109. Esposito K, Pontillo A, DiPalo C, Giugliano G, Masella M, Marfella R et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289: 1799–1804.

    Article  CAS  PubMed  Google Scholar 

  110. Gnacińska M, Małgorzewicz S, Guzek M, Lysiak-Szydłowska W, Sworczak K . Adipose tissue activity in relation to overweight or obesity. Endokrynol Pol 2010; 61: 160–168.

    PubMed  Google Scholar 

  111. Corica F, Allegra A, Corsonello A, Buemi M, Calapai G, Ruello A et al. Relationship between plasma leptin levels and the tumor necrosis factor-alpha system in obese subjects. Int J Obes (Lond) 1999; 23: 355–360.

    Article  CAS  Google Scholar 

  112. Dedoussis G, Kapiri A, Samara A, Dimitriadis D, Lambert D, Pfister M et al. Expression of inflammatory molecules and associations with BMI in children. Eur J Clin Invest 2010; 40: 388–392.

    Article  CAS  PubMed  Google Scholar 

  113. van Dielen F, van’t Veer C, Schols A, Soeters P, Buurman W, Greve J . Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. Int J Obesity 2001; 25: 1759–1766.

    Article  CAS  Google Scholar 

  114. Zhang H, Kumar S, Barnett A, Eggo M . Tumor necrosis factor-a exerts dual effects on human adipose leptin synthesis and release. Mol Cell Endocrinol 1999; 159: 79–88.

    Article  Google Scholar 

  115. Kern P, Saghizadeh M, Ong J, Bosch RJ, Deem R, Simsolo RB . The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss and relationship to lipoprotein lipasa. J Clin Invest 1995; 95: 2111–2119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kirchgessen T, Uysal K, Wiesbrock S, Marino M, Hotamisligil G . Tumor necrosis factor-alpha contributes to obesityrelated hyperleptinemia by regulation leptin release from adipocytes. J Clin Invest 1997; 100: 2777–2782.

    Article  Google Scholar 

  117. Schmidt E . Marine n-3 fatty acids and thrombosis. Thromb Res 2003; 111: 9–10.

    Article  CAS  PubMed  Google Scholar 

  118. Tomas E, Tsao T, Saha A, Murrey H, Zhang C, Itani S et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 2002; 99: 16309–16313.

    Article  CAS  PubMed  Google Scholar 

  119. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762–769.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B Gray.

Ethics declarations

Competing interests

LV received funding from FIT Bioceuticals for the scholarship support of BG. These sponsors had no involvement in the collection, analysis or interpretation of the data; writing the report; or the decision to submit the paper for Publication. LV has received National Institute of Complementary Medicine and National Health and Medical Research Council of Australia competitive funding and Industry support for research into nutraceuticals.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gray, B., Steyn, F., Davies, P. et al. Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management. Eur J Clin Nutr 67, 1234–1242 (2013). https://doi.org/10.1038/ejcn.2013.197

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2013.197

Keywords

This article is cited by

Search

Quick links