(n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: Mechanistic insights

Advances in Nutrition

Volumn 2, Issue 4, 2011, Pages 304-316

  Kalupahana, Nishan S ^a,b,c   Claycombe, Kate J ^d   Moustaid Moussa, Naima ^a,b  

^a UNIVERSITY OF TENNESSEE   (United States)

^b Department of Animal Science ^*  (United States)

^c UNIVERSITY OF PERADENIYA   (Sri Lanka)

^d GRAND FORKS HUMAN NUTRITION RESEARCH CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOCOSAHEXAENOIC ACID; ICOSAPENTAENOIC ACID;

ADIPOSE TISSUE; ANIMAL; HUMAN; INFLAMMATION; INSULIN RESISTANCE; METABOLIC SYNDROME X; METABOLISM; OBESITY; PHYSIOLOGY; RAT; REVIEW;

ADIPOSE TISSUE; ANIMALS; DOCOSAHEXAENOIC ACIDS; EICOSAPENTAENOIC ACID; HUMANS; INFLAMMATION; INSULIN RESISTANCE; METABOLIC SYNDROME X; OBESITY; RATS;

EID: 84655174598     PISSN: 21618313     EISSN: 21565376     Source Type: Journal    
DOI: 10.3945/an.111.000505     Document Type: Review

References (155)

1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120: 1640-5.
2. Chapkin RS, Kim W, Lupton JR, McMurray DN. Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation. Prostaglandins Leukot Essent Fatty Acids. 2009;81:187-91.
3. Flachs P, Rossmeisl M, Bryhn M, Kopecky J. Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci (Lond). 2009;116:1-16.
4. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002; 106:2747-57.
5. Mori TA, Bao DQ, Burke V, Puddey IB, Watts GF, Beilin LJ. 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;70:817-25.
6. Ruzickova J, Rossmeisl M, Prazak T, Flachs P, Sponarova J, Veck M, Tvrzicka E, Bryhn M, Kopecky J. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids. 2004;39:1177-85.
7. Gonzalez-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, Titos E, Martinez-Clemente M, Lopez-Parra M, et al. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 2009;23:1946-57.
8. Storlien LH, Kraegen EW, Chisholm DJ, Ford GL, Bruce DG, Pascoe WS. Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science. 1987;237:885-8.
9. Ghafoorunissa, Ibrahim A, Rajkumar L, Acharya V. Dietary (n-3) long chain polyunsaturated fatty acids prevent sucrose-induced insulin resistance in rats. J Nutr. 2005;135:2634-8.
10. Kabir M, Skurnik G, Naour N, Pechtner V, Meugnier E, Rome S, Quignard-Boulange A, Vidal H, Slama G, et al. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr. 2007;86:1670-9.
11. Rivellese AA, Maffettone A, Iovine C, Di Marino L, Annuzzi G, Mancini M, Riccardi G. Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care. 1996;19:1207-13.
12. Hendrich S. (n-3) Fatty acids: clinical trials in people with type 2 diabetes. Advances in Nutrition. 2010; 1:5.
13. Nettleton JA, Katz R. n-3 Long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc. 2005;105:428-40.
14. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11:11-8.
15. Kim S, Moustaid-Moussa N. Secretory, endocrine and autocrine/paracrine function of the adipocyte. J Nutr. 2000;130:S3110-5.
16. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219-46.
17. Alexaki VI, Notas G, Pelekanou V, Kampa M, Valkanou M, Theodoropoulos P, Stathopoulos EN, Tsapis A, Castanas E. Adipocytes as immune cells: differential expression of TWEAK, BAFF, and APRIL and their receptors (Fn14, BAFF-R, TACI, and BCMA) at different stages of normal and pathological adipose tissue development. J Immunol. 2009;183:5948-56.
18. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821-30.
19. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111-9.
20. Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol. 2008; 216:3-13.
21. Harkins JM, Moustaid-Moussa N, Chung YJ, Penner KM, Pestka JJ, North CM, Claycombe KJ. Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice. J Nutr. 2004;134:2673-7.
22. Zhou HR, Kim EK, Kim H, Claycombe KJ. Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1. Am J Physiol Endocrinol Metab. 2007;293:E1153-8.
23. Chavey C, Mari B, Monthouel MN, Bonnafous S, Anglard P, Van Obberghen E, Tartare-Deckert S. Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J Biol Chem. 2003;278:11888-96.
24. Maquoi E, Munaut C, Colige A, Collen D, Lijnen HR. Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. Diabetes. 2002;51:1093-101.
25. Kos K, Wilding JP. SPARC: a key player in the pathologies associated with obesity and diabetes. Nat Rev Endocrinol. 2010;6:225-35.
26. Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007;293: E1118-28.
27. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes. 2009; 58:718-25.
28. Boden G, Duan X, Homko C, Molina EJ, Song W, Perez O, Cheung P, Merali S. Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes. 2008;57:2438-44.
29. Nakatani Y, Kaneto H, Kawamori D, Yoshiuchi K, Hatazaki M, Matsuoka TA, Ozawa K, Ogawa S, Hori M, et al. Involvement of endoplasmic reticulum stress in insulin resistance and diabetes. J Biol Chem. 2005;280:847-51.
30. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306:457-61.
31. Shen X, Zhang K, Kaufman RJ. The unfolded protein response: a stress signaling pathway of the endoplasmic reticulum. J Chem Neuroanat. 2004;28:79-92.
32. Magne J, Mariotti F, Fischer R, Mathe V, Tome D, Huneau JF. Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue. J Nutr Biochem. 2010;21:550-5.
33. Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr. 2009;139: 1-4.
34. LaRosa PC, Miner J, Xia Y, Zhou Y, Kachman S, Fromm ME. Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis. Physiol Genomics. 2006;27:282-94.
35. Poirier H, Shapiro JS, Kim RJ, Lazar MA. Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes. 2006;55:1634-41.
36. Bes-Houtmann S, Roche R, Hoareau L, Gonthier MP, Festy F, Caillens H, Gasque P, Lefebvre D'Hellencourt C, Cesari M. Presence of functional TLR2 and TLR4 on human adipocytes. Histochem Cell Biol. 2007;127:131-7.
37. Suganami T, Mieda T, Itoh M, Shimoda Y, Kamei Y, Ogawa Y. Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem Biophys Res Commun. 2007;354:45-9.
38. Ehses JA, Meier DT, Wueest S, Rytka J, Boller S, Wielinga PY, Schraenen A, Lemaire K, Debray S, et al. Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet. Diabetologia. 2010;53:1795-806.
39. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17:179-88.
40. Abe M, Matsuda M, Kobayashi H, Miyata Y, Nakayama Y, Komuro R, Fukuhara A, Shimomura I. Effects of statins on adipose tissue inflammation: their inhibitory effect on MyD88-independent IRF3/IFN-beta pathway in macrophages. Arterioscler Thromb Vasc Biol. 2008;28: 871-7.
41. DeFuria J, Bennett G, Strissel KJ, Perfield JW II, Milbury PE, Greenberg AS, Obin MS. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J Nutr. 2009;139:1510-6.
42. Kalupahana NS, Claycombe K, Newman SJ, Stewart T, Siriwardhana N, Matthan N, Lichtenstein AH, Moustaid-Moussa N. Eicosapentaenoic acid prevents and reverses insulin resistance in high-fat dietinduced obese mice via modulation of adipose tissue inflammation. J Nutr. 2010;140:1915-22.
43. Kalupahana NS, Voy BH, Saxton AM, Moustaid-Moussa N. Energyrestricted high-fat diets only partially improve markers of systemic and adipose tissue inflammation. Obesity (Silver Spring). 2011;19: 245-54.
44. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796-808.
45. Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3:23-35.
46. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677-86.
47. Zeyda M, Stulnig TM. Adipose tissue macrophages. Immunol Lett. 2007;112:61-7.
48. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117: 175-84.
49. Prieur X, Mok CY, Velagapudi VR, Nunez V, Fuentes L, Montaner D, Ishikawa K, Camacho A, Barbarroja N, et al. Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes. 2011;60: 797-809.
50. Zeyda M, Farmer D, Todoric J, Aszmann O, Speiser M, Gyori G, Zlabinger GJ, Stulnig TM. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond). 2007;31:1420-8.
51. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008; 57:3239-46.
52. Sato C, Shikata K, Hirota D, Sasaki M, Nishishita S, Miyamoto S, Kodera R, Ogawa D, Tone A, et al. P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance. Diabetes. 2011;60: 189-99.
53. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116:1494-505.
54. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW Jr. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006;116: 115-24.
55. Surmi BK, Webb CD, Ristau AC, Hasty AH. Absence of macrophage inflammatory protein-1{alpha} does not impact macrophage accumulation in adipose tissue of diet-induced obese mice. Am J Physiol Endocrinol Metab. 2010;299:E437-45.
56. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92:1023-33.
57. Eiras S, Teijeira-Fernandez E, Salgado-Somoza A, Couso E, Garcia-Caballero T, Sierra J, Juanatey JR. Relationship between epicardial adipose tissue adipocyte size and MCP-1 expression. Cytokine. 2010;51: 207-12.
58. Lumeng CN, Maillard I, Saltiel AR. T-ing up inflammation in fat. Nat Med. 2009;15:846-7.
59. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15:914-20.
60. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930-9.
61. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15:921-9.
62. Schenk S, Saberi M, Olefsky JM. Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest. 2008;118:2992-3002.
63. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333-46.
64. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006; 7:85-96.
65. Cheng Z, Tseng Y, White MF. Insulin signaling meets mitochondria in metabolism. Trends Endocrinol Metab. 2010;21:589-98.
66. Emanuelli B, Peraldi P, Filloux C, Chavey C, Freidinger K, Hilton DJ, Hotamisligil GS, Van Obberghen E. SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-alpha in the adipose tissue of obese mice. J Biol Chem. 2001;276:47944-9.
67. Zick Y. Ser/Thr phosphorylation of IRS proteins: a molecular basis for insulin resistance. Sci STKE. 2005;2005:pe4.
68. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183-90.
69. Rui L, Yuan M, Frantz D, Shoelson S, White MF. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277:42394-8.
70. Ueki K, Fruman DA, Yballe CM, Fasshauer M, Klein J, Asano T, Cantley LC, Kahn CR. Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling. J Biol Chem. 2003;278:48453-66.
71. Kalupahana NS, Voy BH, Fletcher S, Stewart T, Kim JH, Quignard-Boulange A, Wasserman D, Moustaid-Moussa N. Mechanisms linking overproduction of angiotensinogen by adipose tissue to inflammation, glucose intolerance and insulin resistance. Obesity. 2009;17(suppl 2): S58.
72. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87-91.
73. Luo N, Liu J, Chung BH, Yang Q, Klein RL, Garvey WT, Fu Y. Macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis. Diabetes. 2010;59: 791-9.
74. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature. 2002;420:333-6.
75. ArkanMC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, et al. IKK-beta links inflammation to obesityinduced insulin resistance. Nat Med. 2005;11:191-8.
76. Zhang X, Xu A, Chung SK, Cresser JH, Sweeney G, Wong RL, Lin A, Lam KS. Selective inactivation of c-Jun NH2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice. Diabetes. 2011;60: 486-95.
77. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941-6.
78. Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, KnowlerWC, KrakoffJ. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet. 2002;360:57-8.
79. Brooks GC, Blaha MJ, Blumenthal RS. Relation of C-reactive protein to abdominal adiposity. Am J Cardiol. 2010;106:56-61.
80. Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B, Jung DY, Ko HJ, Ong H, Kim JK, et al. Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure. J Biol Chem. 2010;285:4637-44.
81. Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K, Balletshofer B, Machicao F, Fritsche A, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008;168:1609-16.
82. Gustafson B, Gogg S, Hedjazifar S, Jenndahl L, Hammarstedt A, Smith U. Inflammation and impaired adipogenesis in hypertrophic obesity in man. Am J Physiol Endocrinol Metab. Epub 2009 Jul 21.
83. Stratford S, DeWald DB, Summers SA. Ceramide dissociates 39-phosphoinositide production from pleckstrin homology domain translocation. Biochem J. 2001;354:359-68.
84. Schmitz-Peiffer C. Targeting ceramide synthesis to reverse insulin resistance. Diabetes. 2010;59:2351-3.
85. Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol. Epub 2011 Jan 29.
86. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). 2008;233:674-88.
87. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011;93: 950-62.
88. Aarsetoey H, Aarsetoey R, Lindner T, Staines H, Harris WS, Nilsen DW. Low levels of the omega-3 index are associated with sudden cardiac arrest and remain stable in survivors in the subacute phase. Lipids. 2011;46:151-61.
89. Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord. 1997;21:637-43.
90. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, Ruzickova J, Kopecky J. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia. 2006;49:394-7.
91. Flachs P, Horakova O, Brauner P, Rossmeisl M, Pecina P, Franssen-van Hal N, Ruzickova J, Sponarova J, Drahota Z, et al. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia. 2005;48: 2365-75
92. Van Schothorst EM, Flachs P, Franssen-van Hal NL, Kuda O, Bunschoten A, MolthoffJ, Vink C, Hooiveld GJ, Kopecky J, et al. Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet. BMC Genomics. 2009;10:110.
93. Guo W, Xie W, Lei T, Hamilton JA. Eicosapentaenoic acid, but not oleic acid, stimulates beta-oxidation in adipocytes. Lipids. 2005;40: 815-21.
94. Wensaas AJ, Rustan AC, Just M, Berge RK, Drevon CA, Gaster M. Fatty acid incubation of myotubes from humans with type 2 diabetes leads to enhanced release of beta-oxidation products because of impaired fatty acid oxidation: effects of tetradecylthioacetic acid and eicosapentaenoic acid. Diabetes. 2009;58:527-35.
95. Figueras M, Olivan M, Busquets S, Lopez-Soriano FJ, Argiles JM. Effects of eicosapentaenoic Acid (EPA) treatment on insulin sensitivity in an animal model of diabetes: improvement of the inflammatory status. Obesity (Silver Spring). 2011;19:362-9.
96. Lorente-Cebrian S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond). 2009;117:243-9.
97. Ide T. Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue. Diabetes. 2005;54:412-23.
98. Krebs JD, Browning LM, McLean NK, Rothwell JL, Mishra GD, Moore CS, Jebb SA. Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. Int J Obes (Lond). 2006;30:1535-44.
99. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, Kawano H, Yano T, Aoe S, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol. 2007;27: 1918-25.
100. Kuda O, Jelenik T, Jilkova Z, Flachs P, Rossmeisl M, Hensler M, Kazdova L, Ogston N, Baranowski M, et al. n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia. 2009;52: 941-51.
101. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006;55:924-8.
102. Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Baena MJ, Marti A, Martinez JA, Moreno-Aliaga MJ. Differential inflammatory status in rats susceptible or resistant to diet-induced obesity: effects of EPA ethyl ester treatment. Eur J Nutr. 2008;47:380-6.
103. Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Martinez JA, Moreno-Aliaga MJ. Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats. Br J Nutr. 2009;101:1059-67.
104. Puglisi MJ, Hasty AH, Saraswathi V. The role of adipose tissue in mediating the beneficial effects of dietary fish oil. J Nutr Biochem. 2011; 22:101-8.
105. Todoric J, Loffler M, Huber J, Bilban M, Reimers M, Kadl A, Zeyda M, Waldhausl W, Stulnig TM. Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids. Diabetologia. 2006;49:2109-19.
106. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142:687-98.
107. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, Ogi K, Hosoya M, Tanaka Y, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature. 2003;422: 173-6.
108. Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature. 2007;447: 869-74.
109. White PJ, Arita M, Taguchi R, Kang JX, Marette A. Transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat-fed mice. Diabetes. 2010;59:3066-73.
110. Kim S, Whelan J, Claycombe K, Reath DB, Moustaid-Moussa N. Angiotensin II increases leptin secretion by 3T3-L1 and human adipocytes via a prostaglandin-independent mechanism. J Nutr. 2002;132: 1135-40.
111. Wortman P, Miyazaki Y, Kalupahana NS, Kim S, Hansen-Petrik M, Saxton AM, Claycombe KJ, Voy BH, Whelan J, et al. n3 and n6 Polyunsaturated fatty acids differentially modulate prostaglandin E secretion but not markers of lipogenesis in adipocytes. Nutr Metab (Lond). 2009;6:5.
112. Hsueh HW, Zhou Z, Whelan J, Allen KGD, Moustaid-Moussa N, Kim H, Claycombe KJ. Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via tolllike receptor-2 mediated pathway1. J Nutr. Epub 2011 May 11.
113. Rustan AC, Nossen JO, Christiansen EN, Drevon CA. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. J Lipid Res. 1988;29:1417-26.
114. Saraswathi V, Gao L, Morrow JD, Chait A, Niswender KD, Hasty AH. Fish oil increases cholesterol storage in white adipose tissue with concomitant decreases in inflammation, hepatic steatosis, and atherosclerosis in mice. J Nutr. 2007;137:1776-82.
115. Pettinelli P, Del Pozo T, Araya J, Rodrigo R, Araya AV, Smok G, Csendes A, Gutierrez L, Rojas J, et al. Enhancement in liver SREBP-1c/PPARalpha ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim Biophys Acta. 2009;1792:1080-6.
116. Sekiya M, Yahagi N, Matsuzaka T, Najima Y, Nakakuki M, Nagai R, Ishibashi S, Osuga J, Yamada N, et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology. 2003;38:1529-39.
117. Madsen L, Rustan AC, Vaagenes H, Berge K, Dyroy E, Berge RK. Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference. Lipids. 1999;34:951-63.
118. Teran-Garcia M, Adamson AW, Yu G, Rufo C, Suchankova G, Dreesen TD, Tekle M, Clarke SD, Gettys TW. Polyunsaturated fatty acid suppression of fatty acid synthase (FASN): evidence for dietary modulation of NF-Y binding to the Fasn promoter by SREBP-1c. Biochem J. 2007;402:591-600.
119. Dentin R, Benhamed F, Pegorier JP, Foufelle F, Viollet B, Vaulont S, Girard J, Postic C. Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation. J Clin Invest. 2005;115:2843-54.
120. Hein GJ, Bernasconi AM, Montanaro MA, Pellon-Maison M, Finarelli G, Chicco A, Lombardo YB, Brenner RR. Nuclear receptors and hepatic lipidogenic enzyme response to a dyslipidemic sucrose-rich diet and its reversal by fish oil n-3 polyunsaturated fatty acids. Am J Physiol Endocrinol Metab. 2010;298:E429-39.
121. Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, et al. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol. 2006;169: 846-60.
122. Neschen S, Moore I, Regittnig W, Yu CL, Wang Y, Pypaert M, Petersen KF, Shulman GI. Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab. 2002;282:E395-401.
123. Suchankova G, Tekle M, Saha AK, Ruderman NB, Clarke SD, Gettys TW. Dietary polyunsaturated fatty acids enhance hepatic AMPactivated protein kinase activity in rats. Biochem Biophys Res Commun. 2005;326:851-8.
124. Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, et al. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes. 2007;56:1034-41.
125. Jelenik T, Rossmeisl M, Kuda O, Jilkova ZM, Medrikova D, Kus V, Hensler M, Janovska P, Miksik I, et al. AMP-activated protein kinase alpha2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids. Diabetes. 2010;59:2737-46.
126. Aas V, Rokling-Andersen MH, Kase ET, Thoresen GH, Rustan AC. Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells. J Lipid Res. 2006;47:366-74.
127. Storlien LH, Jenkins AB, Chisholm DJ, Pascoe WS, Khouri S, Kraegen EW. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes. 1991;40:280-9.
128. Kusunoki M, Tsutsumi K, Hara T, Ogawa H, Nakamura T, Miyata T, Sakakibara F, Fukuzawa Y, Suga T, et al. Ethyl icosapentate (omega-3 fatty acid) causes accumulation of lipids in skeletal muscle but suppresses insulin resistance in OLETF rats. Otsuka Long-Evans Tokushima Fatty. Metabolism. 2003;52:30-4.
129. Sinha S, Perdomo G, Brown NF, O'Doherty RM. Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear localization of nuclear factor kappa B. J Biol Chem. 2004;279:41294-301.
130. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763-70.
131. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996;271:10697-703.
132. McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S. Resistin, central obesity, and type 2 diabetes. Lancet. 2002;359:46-7.
133. Jones BH, Standridge MK, Taylor JW, Moustaid N. Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. Am J Physiol. 1997;273: R236-42.
134. Massiera F, Bloch-Faure M, Ceiler D, Murakami K, Fukamizu A, Gasc JM, Quignard-Boulange A, Negrel R, Ailhaud G, et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 2001;15:2727-9.
135. Yvan-Charvet L, Quignard-Boulange A. Role of adipose tissue reninangiotensin system in metabolic and inflammatory diseases associated with obesity. Kidney Int. 2011;79:162-8.
136. Takahashi K, Mizuarai S, Araki H, Mashiko S, Ishihara A, Kanatani A, Itadani H, Kotani H. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem. 2003;278:46654-60.
137. Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes (Lond). 2005;29:146-50.
138. Morange PE, Alessi MC, Verdier M, Casanova D, Magalon G, Juhan-Vague I. PAI-1 produced ex vivo by human adipose tissue is relevant to PAI-1 blood level. Arterioscler Thromb Vasc Biol. 1999;19:1361-5.
139. Mohamed-Ali V, Flower L, Sethi J, Hotamisligil G, Gray R, Humphries SE, York DA, Pinkney J. beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab. 2001;86:5864-9.
140. Lira FS, Rosa JC, Yamashita AS, Koyama CH, Batista ML Jr, Seelaender M. Endurance training induces depot-specific changes in IL-10/TNFalpha ratio in rat adipose tissue. Cytokine. 2009;45:80-5.
141. Frydelund-Larsen L, Akerstrom T, Nielsen S, Keller P, Keller C, Pedersen BK. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise. Am J Physiol Endocrinol Metab. 2007;292:E24-31.
142. Castan-Laurell I, Vitkova M, Daviaud D, Dray C, Kovacikova M, Kovacova Z, Hejnova J, Stich V, Valet P. Effect of hypocaloric dietinduced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ. Eur J Endocrinol. 2008;158:905-10.
143. Kloting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, Fasshauer M, Schon MR, Stumvoll M, et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab. 2007;6:79-87.
144. Gealekman O, Burkart A, Chouinard M, Nicoloro SM, Straubhaar J, Corvera S. Enhanced angiogenesis in obesity and in response to PPARgamma activators through adipocyte VEGF and ANGPTL4 production. Am J Physiol Endocrinol Metab. 2008;295:E1056-64.
145. Peeraully MR, Jenkins JR, Trayhurn P. NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines. Am J Physiol Endocrinol Metab. 2004;287:E331-9.
146. Juge-Aubry CE, Somm E, Chicheportiche R, Burger D, Pernin A, Cuenod-Pittet B, Quinodoz P, Giusti V, Dayer JM, et al. Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue. J Clin Endocrinol Metab. 2004; 89:2652-8.
147. Kloting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun. 2006;339:430-6.
148. Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab. 2006; 290:E1253-61.
149. Kos K, Harte AL, James S, Snead DR, O'Hare JP, McTernan PG, Kumar S. Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass. Am J Physiol Endocrinol Metab. 2007;293:E1335-40.
150. Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, Iannelli A, Staccini-Myx A, Casanova D, et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology. 2006;131:788-96.
151. Bruun JM, Pedersen SB, Richelsen B. Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. J Clin Endocrinol Metab. 2001;86:1267-73.
152. Wood IS, Wang B, Jenkins JR, Trayhurn P. The pro-inflammatory cytokine IL-18 is expressed in human adipose tissue and strongly upregulated by TNFalpha in human adipocytes. Biochem Biophys Res Commun. 2005;337:422-9.
153. Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, Nolen GT, Kern EM, Nagarajan R, Spencer HJ III, et al. Thrombospondin-1 an adipokine associated with obesity, adipose inflammation, and insulin resistance. Diabetes. 2008;57:432-9.
154. Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, Nicklas BJ, Snitker S, Horenstein RB, Hull K, et al. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications. PLoS Med. 2006;3:e287.
155. Becker M, Rabe K, Lebherz C, Zugwurst J, Goke B, Parhofer KG, Lehrke M, Broedl UC. Expression of human chemerin induces insulin resistance in the skeletal muscle but does not affect weight, lipid levels, and atherosclerosis in LDL receptor knockout mice on high-fat diet. Diabetes. 2010;59:2898-903.