Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-22T16:35:20.452Z Has data issue: false hasContentIssue false

The metabolic syndrome: the crossroads of diet and genetics

Published online by Cambridge University Press:  07 March 2007

Helen M. Roche*
Affiliation:
Nutrigenomics Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, 8, Republic of Ireland
Catherine Phillips
Affiliation:
Nutrigenomics Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, 8, Republic of Ireland
Michael J. Gibney
Affiliation:
Nutrigenomics Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, 8, Republic of Ireland
*
*Corresponding author: Dr Helen M. Roche, fax +353 1 4542043, [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The metabolic syndrome is a very common disease associated with an increased risk of type 2 diabetes mellitus (T2DM) and CVD. The clinical characteristics of the metabolic syndrome include insulin resistance, dyslipidaemia, abdominal obesity and hypertension. The diverse clinical characteristics illustrate the complexity of the disease process, which involves several dysregulated metabolic pathways. Thus, multiple genetic targets must be involved in the pathogenesis and progression of the metabolic syndrome. Nevertheless, the human genome has not changed markedly in the last decade but the prevalence of the metabolic syndrome has increased exponentially, which illustrates the importance of gene–environmental interactions. There is good evidence that nutrition plays an important role in the development and progression of the metabolic syndrome. Indeed, obesity is a key aetiological factor in the development of the metabolic syndrome. Understanding the biological impact of gene–nutrient interactions will provide a key insight into the pathogenesis and progression of diet-related polygenic disorders, including the metabolic syndrome. The present paper will explore the interactions between genetic background and dietary exposure or nutritional therapy, focusing on the role of dietary fatty acids within the context of nutrient regulation of gene expression and individual responsiveness to dietary therapy. Only with a full understanding of gene–gene, gene–nutrient and gene–nutrient–environment interactions can the molecular basis of the metabolic syndrome be solved to minimise the adverse health effects of obesity and reduce the risk of the metabolic syndrome, and subsequent T2DM and CVD.

Type
Meeting Report
Copyright
Copyright © The Nutrition Society 2005

References

Aguilera, AA, Diaz, GH, Barcelata, ML, Guerrero, OA & Ros, RM (2004) Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha 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
Al-Shaer, MH & Abusabha, H (2005) The impact of ethnicity on the lifetime risk of the metabolic syndrome and diabetes mellitus. American Journal of Cardiology 95, 819820.CrossRefGoogle ScholarPubMed
Altshuler, D, Hirschhorn, JN, Klannemark, M, Lindgren, CM, Vohl, MC, Nemesh, J et al. . (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genetics 26, 7680.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 et al. . (1999) Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402, 880883.CrossRefGoogle ScholarPubMed
Barroso, I, Luan, J, Middelberg, RP, Harding, AH, Franks, PW, Jakes, RW, Clayton, D, Schafer, AJ, O'Rahilly, S & Wareham, NJ (2003) Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. Public Library of Science Biology 1, 4155.Google ScholarPubMed
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
Clement, K, Hercberg, S, Passinge, B, Galan, P, Varroud-Vial, M, Shuldiner, AR, Beamer, BA, Charpentier, G, Guy-Grand, B, Froguel, P & Vaisse, C (2000) The Pro115Gln and Pro12Ala PPARγ gene mutations in obesity and type 2 diabetes. International Journal of Obesity and Related Metabolic Disorders 24, 391393.CrossRefGoogle ScholarPubMed
Deeb, SS, Fajas, L, Nemoto, M, Pihlajamaki, J, Mykkanen, L, Kuusisto, J, Laakso, M, Fujimoto, W & Auwerx, J (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genetics 20, 284287.CrossRefGoogle ScholarPubMed
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of The Third Report of the National Cholesterol Education Programme (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
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
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.Google Scholar
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
Florez, JC, Hirschhorn, J & Altshuler, D (2003) The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annual Review of Genomics and Human Genetics 4, 257291.CrossRefGoogle ScholarPubMed
Ford, ES, Giles, WH & Dietz, WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. Journal of the American Medical Association 287, 356359.CrossRefGoogle ScholarPubMed
Ford, ES, Giles, WH & Mokdad, AH (2004) Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes 27, 24442449.Google ScholarPubMed
Franks, PW, Luan, J, Browne, PO, Harding, AH, O'Rahilly, S, Chatterjee, VK & Wareham, NJ (2004) Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level. Metabolism 53, 1116.CrossRefGoogle ScholarPubMed
Freeman, MS, Mansfield, MJ, Barrett, JH & Grant, PJ (2002) Heritability of features of the insulin resistance syndrome in a community-based study of healthy families. Diabetic Medicine 19, 994999.CrossRefGoogle Scholar
Groop, L (2000) Genetics of the metabolic syndrome. British Journal of Nutrition 83, Suppl. 1 S39S48.CrossRefGoogle ScholarPubMed
Hara, K, Okada, T, Tobe, K, Yasuda, K, Mori, Y, Kadowaki, H, Hagura, R, Akanuma, Y, Kimura, S, Ito, C & Kadowaki, T (2000) The Pro12Ala polymorphism in PPARγ2 may confer resistance to type 2 diabetes. Biochemical and Biophysical Research Communications 271, 212216.CrossRefGoogle ScholarPubMed
Harding, HA, Day, NE, Khaw, KT, Bingham, S, Luben, R, Welsh, A & Wareham, NJ (2004) Dietary fat and the risk of clinical type 2 diabetes. The European Prospective Investigation of Cancer-Norfolk Study. American Journal of Epidemiology 159, 7382.CrossRefGoogle ScholarPubMed
Hirschhorn, JN, Lohmueller, K, Byrne, E & Hirschhorn, K (2002) A comprehensive review of genetic association studies. Genetics in Medicine 4, 4561.Google Scholar
Horikawa, Y, Oda, N, Cox, NJ, Li, X, Orho-Melander, M, Hara, M et al. . (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nature Genetics 26, 163175.CrossRefGoogle ScholarPubMed
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
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. Diabetic Medicine 19, 456464.CrossRefGoogle ScholarPubMed
Le Marchand-Brustel, Y, Gaul, P, Gremeaux, T, Gonzalez, T, Barres, R & Tanti, JF (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
Lindi, VI, Uusitupa, MI, Lindstrom, J, Louheranta, A, Eriksson, JG, Valle, TT, Hamalainen, H, Ilanne-Parikka, P, Keinanen-Kiukaanniemi, S, Laakso, M & Tuomilehto, J (2002) Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 51, 25812586.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
Mancini, FP, Vaccaro, O, Sabatino, L, Tufano, A, Rivellese, AA, Riccardi, G & Colantuoni, V (1999) Pro12Ala substitution in the peroxisome proliferator-activated receptor-γ2 is not associated with type 2 diabetes. Diabetes 48, 14661468.Google Scholar
Meirhaeghe, A, Fajas, L, Helbecque, N, Cottel, D, Auwerx, J, Deeb, SS & Amouyel, P (2000) Impact of the peroxisome proliferator activated receptor γ2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. International Journal of Obesity and Related Metabolic Disorders 24, 195199.CrossRefGoogle ScholarPubMed
Mills, GW, Avery, PJ, McCarthy, MI, Hattersley, AT, Levy, JC, Hitman, GA, Sampson, M & Walker, M (2004) Heritability estimates for beta cell function and features of the insulin resistance syndrome in UK families with an increased susceptibility to type 2 diabetes. Diabetologia 47, 732738.CrossRefGoogle ScholarPubMed
Perez-Jimenez, F, Lopez-Miranda, J, Pinillos, MD, Gomez, P, Paz-Rojas, E, Montilla, P, Marin, C, Velasco, MJ, Blanco-Molina, A, Jimenez, 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
Poulsen, P, Vaag, A, Kyvik, K, Beck-Nielsen, H (2001) Genetic versus environmental aetiology of the metabolic syndrome among male and female twins. Diabetologia 44, 537543.CrossRefGoogle ScholarPubMed
Rich, SS (1990) Mapping genes in diabetes. Genetic epidemiological perspective. Diabetes 39, 13151319.CrossRefGoogle ScholarPubMed
Ringel, J, Engeli, S, Distler, A & Sharma, AM (1999) Pro12Ala missense mutation of the peroxisome proliferator activated receptor γ and diabetes mellitus. Biochemical and Biophysical Research Communications 254, 450453.CrossRefGoogle ScholarPubMed
Robitaille, J, Despres, JP, Perusse, L & Vohl, MC (2003) The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Quebec Family Study. Clinical Genetics 63, 109116.CrossRefGoogle ScholarPubMed
Roche, HM (2005) Fatty acids and the metabolic syndrome. Proceedings of the Nutrition Society 64, 2329.CrossRefGoogle ScholarPubMed
Roche, HM & Gibney, MJ (2000) The impact of postprandial lipemia in accelerating atherothrombosis. Journal of Cardiovascular Risk 7, 317324.Google Scholar
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
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
Tai, ES, Corella, D, Deurenberg-Yap, M, Adiconis, X, Chew, SK, Tan, CE & Ordovas, JM (2004) Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population. Journal of Lipid Research 45, 674685.CrossRefGoogle Scholar
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
Trayhurn, P & Wood, IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. British Journal of Nutrition 92, 347355.CrossRefGoogle ScholarPubMed
Vessby, B, Unsitupa, 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