Ethnic variation in the activity of lipid desaturases and their relationships with cardiovascular risk factors in control women and an at-risk group with previous gestational diabetes mellitus: a cross-sectional study

Lipids in Health and Disease

Desmond G Johnston¹  Victor Anyaoku¹  Soundarajan Venkatesan¹  Ian F Godsland¹  Mark I McCarthy²  Eleni Kousta¹  Robert G Gray³ 

[1] Diabetes Endocrinology and Metabolic Medicine, Faculty of Medicine, Imperial College London, St. Mary’s Campus, Room G1, Norfolk Place, London W2 1PG, UK;Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK;Diabetes and Nutritional Sciences Division, School of Medicine, King’s College London, London, UK

关键词: Insulin resistance;    HDL cholesterol;    Triglycerides;    Desaturase activities;    Fatty acids;    Delta 5 desaturase;    Delta 6 desaturase;    Stearoyl-CoA desaturase;    Insulin resistance;    Blood pressure;    Lipids;    Ethnicity;   

Others  :  1160064
DOI  :  10.1186/1476-511X-12-25

 received in 2012-09-10, accepted in 2013-02-28,  发布年份 2013

【 摘 要 】

Background

Lipid desaturase enzymes mediate the metabolism of fatty acids to long chain polyunsaturated fatty acids and their activities are related to metabolic risk factors for Type 2 diabetes (T2DM) and coronary heart disease (CHD). There are marked ethnic differences in risks of CHD and T2DM but little is known about ethnic differences in desaturase activities.

Methods

Samples from a study of CVD risk in women with previous gestational diabetes were analysed for percentage fatty acids in plasma free fatty acid, triglyceride, cholesterol ester and phospholipid pools for 89 white European, 53 African Caribbean and 56 Asian Indian women. The fatty acid desaturase activities, stearoyl-CoA desaturase (SCD, calculated separately for C16 and C18 fatty acids), delta 6 desaturase (D6D) and delta 5 desaturase (D5D) were estimated from precursor-to-product ratios and their relationships with adiposity, blood pressure, cholesterol, triglycerides, HDL cholesterol and insulin sensitivity explored. Ethnic differences in desaturase activities independent of ethnic variation in risk factor correlates of desaturase activities were then identified.

Results

There was significant ethnic variation in age, BMI, waist circumference, blood pressure, serum triglycerides and HDL cholesterol concentrations and insulin resistance. Desaturase activities showed significant correlations, independent of ethnicity, with BMI, waist circumference, triglycerides and HDL cholesterol. Independent of ethnic variation in BMI, waist circumference, triglycerides and HDL cholesterol, SCD-16 activity, calculated from each of the four lipid pools measured, was 18–35 percent higher in white Europeans than in African Caribbeans or Asian Indians (all p < 0.001). Similar, though less consistent differences were apparent for SCD-18 activity. Also independently of risk factor variation, but specifically when calculated from the cholesterol ester and phospholipid, pools, D6D activity was significantly lower in Asian Indians, and D5D activity higher in African Caribbeans.

Conclusions

Significant ethnic differences exist in desaturase activities, independently of ethnic variation in other risk factors. These characteristics did not accord with higher risk of T2DM among African Caribbeans and Asian Indians nor with lower risk of CHD among African Caribbeans but did accord with the higher risk of CHD in Asian Indians.

【 授权许可】

   
2013 Gray et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]McKeigue PM, Shah B, Marmot MG: Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991, 337:382-386.
• [2]Wild S, Mckeigue P: Cross sectional analysis of mortality by country of birth in England and Wales, 1970–92. Br Med J 1997, 314:705-710.
• [3]Prospective UK, Diabetes Study Group: Ethnicity and cardiovascular disease. The incidence of myocardial infarction in white, south Asian, and afro-Caribbean patients with type 2 diabetes (UK prospective diabetes study 32). Diabetes Care 1998, 21:1271-1277.
• [4]Mather HM, Chaturvedi N, Fuller JH: Mortality and morbidity from diabetes in South Asians and Europeans: 11-year follow-up of the Southall Diabetes Survey, London, U.K. Diabet Med 1998, 15:53-59.
• [5]Chaturvedi N, McKeigue PM, Marmot MG: Resting and ambulatory blood pressure differences in Afro-Caribbeans and Europeans. Hypertension 1993, 22:90-96.
• [6]Chaturvedi N, Fuller JH: Ethnic differences in mortality from cardiovascular disease in the UK: do they persist in people with diabetes? J Epidemiol Community Health 1996, 50:137-139.
• [7]Chaturvedi N, Jarrett J, Morrish N, Keen H, Fuller JH: Differences in mortality and morbidity in African Caribbean and European people with non-insulin dependent diabetes mellitus: results of 20 year follow up of a London cohort of a multinational study. Br Med J 1996, 313:848-852.
• [8]Zoratti R, Godsland IF, Chaturvedi N, Crook D, Stevenson JC, McKeigue PM: Relation of plasma lipids to insulin resistance, non-esterified fatty acid levels and body fat in men from three ethnic groups: relevance to variation in risk of diabetes and coronary disease. Metabolism 2000, 49:245-252.
• [9]Godsland IF, Johnston DG, Chaturvedi N: Mechanisms of Disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease. Nat Clin Pract Endocrinol Metab 2007, 3:530-538.
• [10]Tillin T, Forouhi NG, Johnston DG, McKeigue PM, Chaturvedi N, Godsland IF: Metabolic syndrome and coronary heart disease in south Asians, African Caribbeans and white Europeans: a U.K. Population-based cross-sectional study. Diabetologia 2005, 48:649-656.
• [11]Attie AD, Krauss RM, Gray-Keller MP, Brownlie A, Miyazaki M, Kastelein JJ, Lusis AJ, Stalenhof AFH, Stoehr JP, Hayden MR, Ntambi JM: Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J Lipid Res 2002, 43:1899-1907.
• [12]Miyazaki M, Kim YC, Gray-Keller MP, Attie AD, Ntambi JM: The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in mice with a disruption of a gene for stearoyl-CoA desaturase. J Biol Chem 2000, 275:30132-30138.
• [13]Vessby B, Gustafsson IB, Tengblad S, Boberg M, Andersson A: Desaturation and elongation of fatty acids and insulin action. Ann NY Acad Sci 2002, 967:183-195.
• [14]Warensjö E, Öhrvall M, Vessby B: Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women. Nutrition, Metab Cardiovasc Dis 2006, 16:128-136.
• [15]Warensjö E, Rosell M, Hellenius ML, Vessby B, De Faire U, Risérus U: Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance. Lipids Health Dis 2009, 8:37. BioMed Central Full Text
• [16]Merino DM, Ma DW, Mutch DM: Genetic variation in lipid desaturases and its impact on the development of human disease. Lipids Health Dis 2010, 9:63. BioMed Central Full Text
• [17]Das UN: A defect in Δ6 and Δ5 desaturases may be a factor in the initiation and progression of insulin resistance, the metabolic syndrome and ischemic heart disease in South Asians. Lipids Health Dis 2010, 9:130. BioMed Central Full Text
• [18]Horrobin DF, Ells K, Morse-Fisher N, Manku MS: Fatty acid distribution in plasma phospholipids in normal individuals from different geographical locations. J Nutr Environ Med 1991, 2:249-258.
• [19]Mathias RA, Sergeant S, Ruczinski I, Torgerson DG, Hugenschmidt CE, Kubala M, Vaidya D, Suktitipat B, Ziegler JT, Ivester P, Case D, Yanek LR, Freedman BI, Rudock ME, Barnes KC, Langefeld CD, Becker LC, Bowden DW, Becker DM, Chilton FH: The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans. BMC Gent 2011, 12:50.
• [20]Sergeant S, Hugenschmidt CE, Rudock ME, Ziegler JT, Ivester P, Ainsworth HC, Vaidya D, Douglas Case L, Langefeld CD, Freedman BI, Bowden DW, Mathias RA, Chilton FH: Differences in arachidonic acid levels and fatty acid desaturase ( FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome. Br J Nutr 2011. epub Jul 4
• [21]Khaw KT, Friesen MD, Riboli E, Luben R, Wareham N: Plasma phospholipid fatty acid concentration and incident coronary heart disease in Men and women: the EPIC-Norfolk prospective study. PLoS Med 2012, 9:e1001255.
• [22]Shiwaku K, Hashimoto M, Kitajima K, Nogi A, Anuurad E, Enkhmaa B, Kim JM, Kim IS, Lee SK, Oyunsuren T, Shido O, Yamane Y: Triglyceride levels are ethnic-specifically associated with an index of stearoyl-CoA desaturase activity and n-3 PUFA levels in Asians. J Lipid Res 2004, 45:914-922.
• [23]Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV: The relation between insulin sensitivity and the fatty acid composition of skeletal-muscle phospholipids. N Engl J Med 1993, 328:238-244.
• [24]Pan DA, Lillioja S, Milner MR, Kriketos AD, Baur LA, Bogardus C, Storlien LH: Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J Clin Invest 1995, 96:2802-2808.
• [25]Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH: Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 2003, 78:91-98.
• [26]Patel PS, Sharp SJ, Jansen E, Luben RN, Khaw KT, Wareham NJ, Forouhi NG: Fatty acids measured in plasma and erythrocyte-membrane phospholipids and derived by food-frequency questionnaire and the risk of new-onset type 2 diabetes: a pilot study in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Am J Clin Nutr 2010, 92:1214-1222.
• [27]Kousta E, Efstathiadou Z, Lawrence NJ, Jeffs JAR, Barrett SC, Doré CJ, Penny A, Anyaoku V, Millauer BA, Cela E, Godsland IF, Robinson S, McCarthy MI, Johnston DG: The impact of ethnicity on glucose regulation and the metabolic syndrome following gestational diabetes. Diabetologia 2006, 49:36-40.
• [28]Chaturvedi N, Marmot MG, McKeigue PM: Racial differences in hypertension. Br Med J 1994, 308:1634-1635.
• [29]Chaturvedi N, McKeigue PM, Marmot MG: Relationship of glucose intolerance to coronary risk in Afro-Caribbeans compared with Europeans. Diabetologia 1994, 37:765-772.
• [30]Proudler AJ, Godsland IF, Bruce R, Seed M, Wynn V: Lipid and carbohydrate metabolic risk markers for coronary heart disease, and blood pressure in non-obese healthy women of different ethnic origin. Metabolism 1996, 45:328-333.
• [31]Kousta E, Lawrence NJ, Godsland IF, Penny A, Anyaoku V, Millauer BA, Cela E, Johnston DG, Robinson S, McCarthy MI: Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes. Clin Endocrinol 2003, 59:289-297.
• [32]Venkatesan S, Rideout JM, Simpson KJ: Microsomal delta 9, delta 6 and delta 5 desaturase activities and liver membrane fatty acid profiles in alcohol-fed rats. Biomed Chromatogr 1990, 4:234-238.
• [33]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28:412-419.
• [34]Perneger TV: What’s wrong with Bonferroni adjustments. BMJ 1997, 316:1236-1238.