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Fatty acids and the metabolic syndrome

Published online by Cambridge University Press:  07 March 2007

Helen M. Roche
Nutrigenomics Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin, Republic of Ireland
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The metabolic syndrome is a very common condition, characterised by insulin resistance, dyslipidaemia, abdominal obesity and hypertension, that is associated with a high risk of type 2 diabetes mellitus (T2DM) and CVD. Obesity is a key aetiological factor in the development of the metabolic syndrome. In light of the increasing prevalence of obesity, there is a high requirement to reduce the impact of the adverse health effects associated with the metabolic syndrome. The aetiological role of nutrient-derived metabolic stressors, in particular fatty acids, in the development of obesity and the metabolic syndrome is explored. Also, the evidence that pro-inflammatory stressors may predispose to obesity-induced insulin resistance is reviewed. The present paper explores the concept that reducing the impact of metabolic and inflammatory stressors may reduce the adverse health effects of obesity and slow the progression towards the metabolic syndrome and T2DM. Evidence from human dietary intervention studies that have investigated the potential therapeutic effects of dietary fatty acid modification is explored. The present review highlights the requirement to take account of genetic background, within the context of nutrient regulation of gene expression and individual responsiveness to dietary therapy. This approach will further the understanding of the interaction between fatty acids in the pathogenesis and progression of the metabolic syndrome.

Symposium on ‘Obesity and metabolic diseases’
Copyright © The Nutrition Society 2005


Aguilera, AA, Diaz, GH, Barcelata, ML, Guerrero, OA & Ros, RMO (2004) Effects of fish oil on hypertension, plasma lipids and tumor necrosis factor-α in rats with sucrose-induced metabolic syndrome. Journal of Nutritional Biochemistry 15, 350357.CrossRefGoogle ScholarPubMed
Alberti, K & Zimmet, P (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabetic Medicine 15, 539553.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Aljada, A, Ghanim, H, Mohanty, P, Kapur, N & Dandona, P (2002) Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. Journal of Clinical Endocrinology and Metabolism 87, 14191422.CrossRefGoogle ScholarPubMed
Barak, Y, Nelson, MC, Ong, ES, Jones, YZ, Ruiz-Lozano, P, Chien, KR, Koder, A & Evans, RM (1999) PPAR gamma is required for placental, cardiac, and adipose tissue development. Molecular Cell 4, 585595.CrossRefGoogle ScholarPubMed
Barroso, I, Gurnell, M, Crowley, VE, Agostini, M, Schwabe, JW, Soos, MA, Maslen, GL, Williams, TD, Lewis, H, Schafer, AJ, Chatterjee, VK & O'Rahilly, S (1999) Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402, 880883.CrossRefGoogle ScholarPubMed
Beamer, BA, Yen, CJ, Andersen, RE, Muller, D, Elahi, D, Cheskin, LJ, Andres, R, Roth, J & Shuldiner, AR (1998) Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian popu-lations. Diabetes 47, 18061808.CrossRefGoogle Scholar
Brady, LM, Lovegrove, SS, Lesauvage, SV, Gower, BA, Minihane, AM, Williams, CM & Lovegrove, JA (2004) Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians. American Journal of Clinical Nutrition 79, 983991.CrossRefGoogle ScholarPubMed
Campos, H, D'Agostino, M & Ordovas, JM (2001) Gene-diet interactions and plasma lipoproteins: role of apolipoprotein E and habitual saturated fat intake. Genetic Epidemiology 20, 117128.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Dandona, P, Aljada, A & Bandyopadhyay, A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. TRENDS in Immunology 25, 47.CrossRefGoogle ScholarPubMed
Dandona, P, Aljada, A, Mohanty, P, Ghanim, H, Hamouda, W, Assian, E & Ahmad, S (2001) Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect. Journal of Clinical Endocrinology and Metabolism 86, 32573265.Google ScholarPubMed
Fasching, P, Ratheiser, K, Waldhausl, W, Rohac, M, Osterrode, W, Nowotny, P & Vierhapper, H (1991) Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance. Diabetes 40, 583589.CrossRefGoogle ScholarPubMed
Fernandez-Real, JM, Lopez-Bermejo, A, Casamitjana, R & Ricart, W (2003) Novel interactions of adiponectin with the endocrine system and inflammatory parameters. Journal of Clinical Endocrinology and Metabolism 88, 27142718.CrossRefGoogle ScholarPubMed
Feskens, EJ, Bowles, CH & Kromhout, D (1991) Inverse association between fish intake and risk of glucose intolerance in normoglycemic elderly men and women. Diabetes Care 14, 935941.CrossRefGoogle ScholarPubMed
Feskens, EJ, Virtanen, SM, Rasanen, L, Tuomilehto, J, Stengard, J, Pekkanen, J, Nissinen, A & Kromhout, D (1985) Dietary factors determining diabetes and impaired glucose tolerance. A 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetes Care 18, 11041112.CrossRefGoogle Scholar
Foretz, M, Guichard, P, Frerre, C & Foufelle, F (1999) Sterol regulatory element-binding protein-1c is a major mediator of insulin action gene expression, a key regulatory transcription factor on the hepatic expression of glucokinase and lipogenesis-related genes. Proceedings of the National Academy of Sciences USA 96, 1273712742.CrossRefGoogle ScholarPubMed
Fruhbeck, G, Gomez-Ambrosi, J, Muruzabal, FJ & Burrell, MA (2001) The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. American Journal of Physiology 280, E827E847.Google ScholarPubMed
Gosmain, Y, Lefai, E, Rysner, S, Roques, M & Vidal, H (2004) Sterol regulatory element-binding protein-1 mediates the effect of insulin on hexokinase II gene expression in human muscle cells. Diabetes 53, 321329.CrossRefGoogle ScholarPubMed
Grimble, RF, Howell, WM, O'Reilly, G, Turner, SJ, Markovic, O, Hirrell, S, East, JM & Calder, PC (2002) The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. American Journal of Clinical Nutrition 76, 454459.CrossRefGoogle ScholarPubMed
Hotamisigil, GS (2003) Inflammatory pathways and insulin action. International Journal of Obesity 27, S53S55.CrossRefGoogle Scholar
Hotamisigil, GS (1999) The role of TNF-alpha and TNF receptors in obesity and insulin resistance. Journal of Internal Medicine 245, 621625.CrossRefGoogle Scholar
Isomaa, B, Almgren, P, Tuomi, T, Forsen, B, Lahti, K, Nissen, M, Taskinen, MR & Groop, L (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24, 683689.CrossRefGoogle ScholarPubMed
Kahn, BB & Flier, JS (2000) Obesity and insulin resistance. Journal of Clinical Investigation 106, 473481.CrossRefGoogle ScholarPubMed
Kim, JK, Kim, YJ, Fillmore, JJ, Chen, Y, Moore, I, Lee, J, Yuan, M, Li, ZW, Karin, M, Perret, P, Shoelson, SE & Shulman, GI (2001) Prevention of fat-induced insulin resistance by salicylate. Journal of Clinical Investigation 108, 437446.CrossRefGoogle ScholarPubMed
King, H, Aubert, RE & Herman, WH (1998) Global burden of diabetes 1995–2025. Diabetes Care 21, 14141431.CrossRefGoogle ScholarPubMed
Knowler, WC, Barrett-Connor, E, Fowler, SE, Hamman, RF, Lachin, JM, Walker, EA & Nathan, DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine 7, 393403.Google Scholar
Kubaszek, A, Pihlajamaki, J, Komarovski, V, Lindi, V, Lindstrom, J & Eriksson, J et al. (2003) Finnish Diabetes Prevention Study. Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 52, 18721876.CrossRefGoogle ScholarPubMed
Laaksonen, DE, Lakkat, TA, Lakkat, H-M, Nyyssonent, K, Rissanent, T, Niskanen, LK & Salonen, JY (2002) Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men. Diabetes Medicine 19, 456464.CrossRefGoogle ScholarPubMed
Le Marchand-Brustel, Y, Gaul, P, Gremeaux, T, Gonzalez, T, Barres, R & Tanti, J-F (2003) Fatty acid-induced insulin resistance: role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling. Biochemical Society Transactions 31, 11521156.CrossRefGoogle ScholarPubMed
Lovejoy, JC, Smith, SR, Champagne, CM, Most, MM, Lefevre, M, DeLany, JP, Denkins, YM, Rood, JC, Veldhuis, J & Bray, GA (2002) Effects of diets enriched in saturated (palmitic), monounsaturated (oleic), or trans (eladic) fatty acids in insulin sensitivity and substrate oxidation in healthy adults. Diabetes Care 25, 12831288.CrossRefGoogle Scholar
Luan, J, Browne, PO, Harding, AH, Halsall, DJ, O'Rahilly, S, Chatterjee, VK & Wareham, NJ (2001) Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes 50, 686689.CrossRefGoogle ScholarPubMed
Lyon, CJ, Law, RE & Hsueh, WA (2003) Adiposity, inflammation and atherogenesis. Endocrinology 144, 21952200.CrossRefGoogle ScholarPubMed
Mann, JI (2002) Diet and risk of coronary heart disease and type 2 diabetes. Lancet 360, 783789.CrossRefGoogle ScholarPubMed
Moloney, F, Noone, E, Loscher, C, Gibney, MJ & Roche, HM (2004) Cis -9, trans -11 conjugated linoleic acid improves metabolic and molecular markers of insulin sensitivity in adipose tissue and liver. Proceedings of the Nutrition Society 63 58A.Google Scholar
National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2001) Executive Summary of The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Journal of the American Medical Association 285, 24862497.CrossRefGoogle Scholar
Peraldi, P & Spiegleman, B (1998) TNF-alpha and insulin resistance: summary and future prospects. Molecular Cell Biochemistry 182, 169175.CrossRefGoogle ScholarPubMed
Perez-Jimenez, E, Lopez-Miranda, J, Pinillos, MD, Gomez, P, Paz-Rojas, E, Montilla, P, Marin, C, Velasco, MJ, Blanco-Molina, A, Jimenez, Pereperez & JA Ordovas, JM (2001) A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons. Diabetologia 44, 20382043.CrossRefGoogle Scholar
Popp-Snijders, C, Schouten, JA, Heine, RJ, van der, Meer, J, van & der Veen, EA (1987) Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes. Diabetes Research 4, 141147.Google ScholarPubMed
Roche, HM & Gibney, MJ (2000) The effect of long-chain n-3 PUFA on fasting and postprandial triacylglycerol metabolism. American Journal of Clinical Nutrition 71, 232237.CrossRefGoogle ScholarPubMed
Roche, HM, Noone, E, Sewter, C, McBennett, S, Savage, D, Gibney, MJ, O'Rahilly, S & Vidal-Puig, AJ (2002) Isomer dependent metabolic effects of conjugated linoleic acid (CLA), insights from molecular markers: SREBP-1c and LXRα. Diabetes 51, 20372044.CrossRefGoogle ScholarPubMed
Saltiel, AR (2000) The molecular and physiological basis of insulin resistance: emerging implications for metabolic and cardiovascular diseases. Journal of Clinical Investigation 106, 163164.CrossRefGoogle ScholarPubMed
Senn, JJ, Klover, PJ, Nowak, IA & Mooney, RA (2002) Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 51, 33913399.CrossRefGoogle ScholarPubMed
Senn, JJ, Klover, PJ, Nowak, IA, Zimmers, TA, Koniaris, LG, Furlanetto, RW & Mooney, RA (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. Journal of Biological Chemistry 278, 1374013746.CrossRefGoogle Scholar
Shimomura, I, Matsuda, M, Hammer, RE, Bashmakov, Y, Brown, MS & Goldstein, JL (2000) Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Molecular Cell 6, 7786.CrossRefGoogle ScholarPubMed
Stefan, N, Wahl, HG, Fritsche, A, Haring, H & Stumvoll, M (2001) Effect of the pattern of elevated free fatty acids on insulin sensitivity and insulin secretion in healthy humans. Hormone Metabolism Research 33, 432438.CrossRefGoogle ScholarPubMed
Steppan, CM, Bailey, ST, Bhat, S, Brown, EJ, Banerjee, RR, Wright, CM, Patel, HR, Ahima, RS & Lazar, MA (2001) The hormone resistin links obesity to diabetes. Nature 409, 307312.CrossRefGoogle ScholarPubMed
Storlien, LH, Kraegen, EW, Chisholm, DJ, Ford, GL, Bruce, DG & Pascoe, WS (1987) Fish oil prevents insulin resistance induced by high fat feeding in rats. Science 237, 885888.CrossRefGoogle ScholarPubMed
Tanasescu, M, Cho, E, Manson, JE & Hu, FB (2004) Dietary fat and cholesterol and the risk of cardiovascular disease among women with type 2 diabetes. American Journal of Clinical Nutrition 79, 99105.CrossRefGoogle ScholarPubMed
Vessby, B, Uusitupa, M, Hermansen, K, Riccardi, G, Rivellese, AA & Tapsell, LC et al. (2001) Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study. Diabetologia 44, 312319.CrossRefGoogle ScholarPubMed
Weisberg, SP, McCann, D, Desai, M, Rosenbaum, M, Leibel, RL & Ferrante AW, Jr (2004) Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112, 17961808.CrossRefGoogle Scholar
Yamauchi, T, Kamon, J, Waki, H, Terauchi, Y, Kubota, N & Hara, K et al. (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Medicine 7, 941946.CrossRefGoogle ScholarPubMed
Zick, Y (2001) Insulin resistance: a phosphorylation-based uncoupling of insulin signalling. TRENDS in Cell Biology 11, 437441.CrossRefGoogle Scholar
Zimmet, P, Alberti, KGMM & Shaw, J (2001) Global and societal implications of the diabetes epidemic. Nature 414, 782787.CrossRefGoogle ScholarPubMed