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n-3 PUFA: bioavailability and modulation of adipose tissue function: Symposium on ‘Frontiers in adipose tissue biology’

  • Jan Kopecky (a1), Martin Rossmeisl (a1), Pavel Flachs (a1), Ondrej Kuda (a1), Petr Brauner (a1), Zuzana Jilkova (a1), Barbora Stankova (a2), Eva Tvrzicka (a2) and Morten Bryhn (a3)...

Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA.

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*Corresponding author: Professor Jan Kopecky, fax +420 241062599, email
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2. SE Kahn , RL Hull & KM Utzschneider (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840846.

3. J Tuomilehto , J Lindstrom , JG Eriksson (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344, 13431350.

5. CH Ruxton , SC Reed , MJ Simpson (2004) The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Diet 17, 449459.

7. P Singer , H Shapiro , M Theilla (2008) Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective. Intensive Care Med 34, 15801592.

8. S Ikemoto , M Takahashi , N Tsunoda (1996) High-fat diet-induced hyperglycemia and obesity in mice: Differential effects of dietary oils. Metabolism 45, 15391546.

9. LH Storlien , EW Kraegen , DJ Chisholm (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237, 885888.

10. P Libby , J Plutzky (2007) Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma agonists. Am J Cardiol 99, 27B40B.

11. J Ruzickova , M Rossmeisl , T Prazak (2004) Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids 39, 11771185.

12. P Flachs , O Horakova , P Brauner (2005) Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 48, 23652375.

13. O Kuda , T Jelenik , Z Jilkova (2009) 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 52, 941951.

15. C Couet , J Delarue , P Ritz (1997) Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes (Lond) 21, 637643.

18. JA Nettleton & R Katz (2005) n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc 105, 428440.

20. JT Brenna , N Salem Jr, AJ Sinclair (2009) alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80, 8591.

22. F Massiera , P Saint-Marc , J Seydoux (2003) Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res 44, 271279.

23. P Flachs , M Rossmeisl , M Bryhn (2009) Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci (Lond) 116, 116.

24. A Gonzalez-Periz , R Horrillo , N Ferre (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J (Epublication ahead of print version; doi: 10.1096/fj.08–125674).

26. JM Schwab , N Chiang , M Arita (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447, 869874.

27. LM Sanderson , PJ de Groot , GJ Hooiveld (2008) Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics. PLoS ONE 3, e1681.

28. S Luquet , C Gaudel , D Holst (2005) Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes. Biochim Biophys Acta 1740, 313317.

29. L Madsen , RK Petersen & K Kristiansen (2005) Regulation of adipocyte differentiation and function by polyunsaturated fatty acids. Biochim Biophys Acta 1740, 266286.

30. S Neschen , K Morino , J Dong (2007) n-3 Fatty acids preserve insulin sensitivity in vivo in a PPAR-alpha-dependent manner. Diabetes 56, 10341041.

31. DB Jump (2004) Fatty acid regulation of gene transcription. Crit Rev Clin Lab Sci 41, 4178.

32. S Neschen , K Morino , JC Rossbacher (2006) Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-dependent mechanism in mice. Diabetes 55, 924928.

33. M Teran-Garcia , AW Adamson , G Yu (2007) 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 402, 591600.

34. EM van Schothorst , P Flachs , NL Franssen-van Hal (2009) Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet. BMC Genomics 10, 110.

35. BM Jucker , GW Cline , N Barucci (1999) Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study. Diabetes 48, 134140.

36. G Suchankova , M Tekle , AK Saha (2005) Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats. Biochem Biophys Res Commun 326, 851858.

37. NK Gabler , JS Radcliffe , JD Spencer (2009) Feeding long-chain n-3 polyunsaturated fatty acids during gestation increases intestinal glucose absorption potentially via the acute activation of AMPK. J Nutr Biochem 20, 1725.

38. D Carling (2004) The AMP-activated protein kinase cascade – a unifying system for energy control. Trends Biochem Sci 29, 1824.

39. DM Muoio & CB Newgard (2008) Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9, 193205.

40. PS Sastry (1985) Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24, 69–176.

41. RB Heath , F Karpe , RW Milne (2003) Selective partitioning of dietary fatty acids into the VLDL TG pool in the early postprandial period. J Lipid Res 44, 20652072.

42. A Covaci , J de Boer , JJ Ryan (2002) Distribution of organobrominated and organochlorinated contaminants in Belgian human adipose tissue. Environ Res 88, 210218.

45. W Stillwell , SR Shaikh , M Zerouga (2005) Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev 45, 559579.

48. C Darimont , G Vassaux , G Ailhaud (1994) Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin-II. Endocrinology 135, 20302036.

49. M Korotkova , B Gabrielsson , M Lonn (2002) Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet. J Lipid Res 43, 17431749.

50. S Arenz , R Ruckerl , B Koletzko (2004) Breast-feeding and childhood obesity – a systematic review. Int J Obes Relat Metab Disord 28, 12471256.

51. M Knip & HK Akerblom (2005) Early nutrition and later diabetes risk. Adv Exp Med Biol 569, 142150.

53. YB Lombardo , G Hein & A Chicco (2007) Metabolic syndrome: effects of n-3 PUFAs on a model of dyslipidemia, insulin resistance and adiposity. Lipids 42, 427437.

54. O Matejkova , KJ Mustard , J Sponarova (2004) Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat. FEBS Lett 569, 245248.

55. L Orci , WS Cook , M Ravazzola (2004) Rapid transformation of white adipocytes into fat-oxidizing machines. Proc Natl Acad Sci U S A 101, 20582063.

56. Y-T Zhou , Z-W Wang , M Higa (1999) Reversing adipocyte differentiation: Implications for treatment of obesity. Proc Natl Acad Sci U S A 96, 23912395.

57. JA Maassen , JA Romijn & RJ Heine (2007) Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus. Diabetologia 50, 20362041.

58. A Okuno , H Tamemoto , K Tobe (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 101, 13541361.

59. J Todoric , M Loffler , J Huber (2006) Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids. Diabetologia 49, 21092119.

61. X Yang & U Smith (2007) Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer? Diabetologia 50, 11271139.

63. U Kintscher & RE Law (2005) PPARgamma-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab 288, E287E291.

64. E Danforth Jr (2000) Failure of adipocyte differentiation causes type II diabetes mellitus? Nature Genetics 26, 13.

65. ED Abel , O Peroni , JK Kim (2001) Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409, 729733.

66. M Rossmeisl , T Jelenik , Z Jilkova (2009) Prevention and reversal of obesity and glucose intolerance in mice by DHA-derivatives. Obesity 17, 10231031.

67. S Cinti , G Mitchell , G Barbatelli (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46, 23472355.

68. CN Lumeng , JB Delproposto , DJ Westcott (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57, 32393246.

70. MA Bouhlel , B Derudas , E Rigamonti (2007) PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6, 137143.

71. AS Rossi , YB Lombardo , JM Lacorte (2005) Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol 289, R486R494.

72. P Flachs , V Mohamed-Ali , O Horakova (2006) Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed high-fat diet. Diabetologia 49, 394397.

73. T Yamauchi , J Kamon , Y Minokoshi (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8, 12881295.

74. AR Nawrocki , MW Rajala , E Tomas (2006) Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 281, 26542660.

75. JD Krebs , LM Browning , NK McLean (2006) 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) 30, 15351544.

76. J Sponarova , KJ Mustard , O Horakova (2005) Involvement of AMP-activated protein kinase in fat depot-specific metabolic changes during starvation. FEBS Lett 579, 61056110.

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