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Biomarkers of dietary fatty acids and metabolism and body mass index: the EPIC-PANACEA Study Véronique Chajès Nutrition and Metabolism International Agency for Research on Cancer 1 1 Fatty acids and obesity -Epidemiology Obesity: a serious health problem worldwide Increase in obesity thought to be due largely to lifestyle factors, such as diet and physical inactivity, along with a genetic component. (de Ferranti and Mozaffarian. Clin Chem 2008;54:945-55) 2 Fatty acids and obesity - Rationale Obesity: a serious health problem worldwide Increase in obesity thought to be due largely to lifestyle factors, such as diet and physical inactivity, along with a genetic component. Fatty acids, overweight and obesity The role of dietary fatty acids in weight gain and obesity remains highly controversial (Melanson et al. Ann Nutr Metab 2009; 55:229-43) 3 Fatty acids and obesity - Rationale Obesity: a serious health problem worldwide Increase in obesity thought to be due largely to lifestyle factors, such as diet and physical inactivity, along with a genetic component. Fatty acids, overweight and obesity The role of dietary fatty acids in weight gain and obesity remains highly controversial Total fatty acids possible positive association Saturated fatty acids (Melanson et al. Ann Nutr Metab 2009; 55:229-43) 4 Fatty acids and obesity - Rationale Obesity: a serious health problem worldwide Increase in obesity thought to be due largely to lifestyle factors, such as diet and physical inactivity, along with a genetic component. Fatty acids, overweight and obesity The role of dietary fatty acids in weight gain and obesity remains highly controversial Total fatty acids possible positive association Saturated fatty acids - Monounsaturated fatty acids PUFA Trans fatty acids evidence less clear (Melanson et al. Ann Nutr Metab 2009; 55:229-43; Jakobsen et al. Obes Facts 2011;4:312-18) 5 Methodological issues • • • • • BMI as indicator of adiposity Dietary measurement error (FFQ vs other reporting instrument) Conversion of food items into their fatty acid content complex Homogeneous populations with a narrow range of fat intakes Limited data on biomarkers of lipid exposure and metabolism 6 What biomarkers of fatty acids may offer Long-term biomarker • • • Adipose tissue (gluteal, breast, etc.) • Triglycerides 2 years Erythrocytes or platelets • Membrane phospholipids 3 months Lipid • • • • fractions in serum or plasma Phospholipids Cholesterol esters Triglycerides Total serum weeks to months weeks hours ? Short-term biomarker 7 Design EPIC - European Prospective Investigation into Cancer and Nutrition (1992-ongoing): • • • Cohort involving 23 centres in 10 European countries (N=520,000) Country-specific dietary questionnaires validated locally Anthropometric data and blood samples were collected at baseline The EPIC Study 8 Design • Cross-sectional analyses on 3,003 subjects who are part of the EPIC sub-calibration study. • Plasma phospholipid fatty acids measured by gas chromatography at the IARC-WHO laboratory. • • Associations between plasma phospholipid fatty acids (% of total fatty acids) and BMI [<25; 2530; >30kg/m2], as indicator of overall obesity. All measurements were adjusted for region, age, menopausal status, alcohol intake, physical activity, smoking status, educational level, and energy intake. The EPIC-PANACEA Study Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity Project 9 Prevalence of obesity (BMI) in the EPICPANACEA Study BMI Umea Athens 30 Granada 25 Murcia Malmo 20 15 Denmark Northern Spain 10 5 UK Health conscious Ragusa/Naples 0 UK General population MEN WOMEN Florence Varese/Turin The Netherlands Potsdam France Heidelberg Overweight and obesity, estimated by BMI measures, are higher in Southern vs Northern centres 10 Saturated fatty acids (diet) and BMI Fatty acids Tertiles P-trend OR* 95%CI 15:0 <.0001 1 1.00 2 0.92 0.74-1.15 3 0.64 0.51-0.81 1 1.00 2 0.71 0.57-0.89 3 0.38 0.30-0.49 17:0 <.0001 0.5 1 *adjusted for region, age, alcohol intake, physical activity, smoking status, educational level, and energy intake 11 Saturated fatty acids (diet/metabolism) and BMI Fatty acids Tertiles OR* P-trend 95%CI 16:0 0.0218 1 1.00 2 1.33 1.07-1.65 3 1.34 1.05-1.71 1 1.00 2 1.47 1.20-1.80 3 2.02 1.61-2.53 18:0 <.0001 1 2 *adjusted for region, age, alcohol intake, physical activity, smoking status, educational level, and energy intake 12 Monounsaturated fatty acids and BMI Fatty acids Tertiles OR* P-trend 95%CI 16:1n7/9t + 18:1n-9t <.0001 1 1.00 2 1.25 1.00-1.58 3 1.71 1.33-2.19 1 1.00 2 1.03 0.84-1.26 3 0.81 0.65-1.02 18:1n9c 0.0809 1 2 *adjusted for region, age, alcohol intake, physical activity, smoking status, educational level, and energy intake 13 Ratios of fatty acids (desaturases) and BMI Fatty acids Tertiles OR* 95%CI 16:1n-7/16:0 ∆-9 desaturase or SCD-1 1 P-trend <.0001 1.00 2 1.39 1.11-1.74 3 1.78 1.39-2.27 1 1.00 2 1.47 1.20-1.80 3 1.90 1.54-2.34 1 1.00 2 0.67 0.55-0.83 3 0.38 0.31-0.48 18:3n-6/18:2n-6 ∆-6 desaturase <.0001 20:4n-6/20:3n-6 ∆-5 desaturase <.0001 0.5 1 2 *adjusted for region, age, alcohol intake, physical activity, smoking status, educational level, and energy intake 14 Conclusion A specific fatty acid profile, as a biomarker of both lipid exposure and fatty acid metabolism, is associated to BMI 15 Conclusion A specific fatty acid profile, as a biomarker of both lipid exposure and fatty acid metabolism, is associated to BMI • Biomarkers of dietary exposure High intake of saturated 15:0 and 17:0 (dairy products) may decrease risk of obesity 16 Conclusion A specific fatty acid profile, as a biomarker of both lipid exposure and fatty acid metabolism, is associated to BMI Biomarkers of dietary exposure • High intake of saturated 15:0 and 17:0 (dairy products) may decrease risk of obesity • High intake of trans fatty acids (industrial trans fatty acids) may increase risk of obesity 17 Conclusion A specific fatty acid profile, as a biomarker of both lipid exposure and fatty acid metabolism, is associated to BMI Biomarkers of dietary exposure • High intake of saturated 15:0 and 17:0 (dairy products) may decrease risk of obesity • High intake of trans fatty acids (industrial trans fatty acids) may increase risk of obesity Biomarkers of fatty acid metabolism • High intake of saturated fatty acids (16:0 and 18:0) along with increased hepatic expression/activity of Δ-9 desaturase may increase risk of obesity 18 Perspectives A specific fatty acid profile, as a biomarker of both lipid exposure and fatty acid metabolism, is associated to BMI Biomarkers of dietary exposure • High intake of saturated 15:0 and 17:0 (dairy products) may decrease risk of obesity • High intake of trans fatty acids (industrial trans fatty acids) may increase risk of obesity Biomarkers of fatty acid metabolism • High intake of saturated fatty acids (16:0 and 18:0) along with increased hepatic expression/activity of Δ-9 desaturase may increase risk of obesity Perspectives • • Association between biomarkers of fatty acids and BMI change Comparison of natural trans fatty acids versus industrial trans fatty acids 19 Acknowledgements IARC, Lyon N. Slimani (DEX) I. Romieu (NEP) P. Ferrari (NEP) Imperial College, London E. Riboli EPIC PIs Financial support European Commission, LNCC, INCA (France) 20