Effects of Macronutrients on Hepatic Lipids, Plasma Triglycerides, and Insulin Sensitivity (MACRONUTR)

Study of the Role of Insulin Resistance in the Pathogenesis of the Metabolic Syndrome and of Non-alcoholic Steatohepatitis

The purpose of this study is to assess how the macronutrient composition of the diet effects lipid and glucose metabolism intrahepatic lipids insulin sensitivity in healthy lean subjects and in subjects with a high metabolic risk (ie overweight and offsprings of patients with type 2 diabetes mellitus).

The study is aimed at assessing the effects of changes in total energy, sugars, lipids, and protein intake on intrahepatic lipids, plasma lipids, and hepatic and whole body insulin resistance in lean men and women with no family history of diabetes overweight men and women lean men with a family history of type 2 diabetes Subjects are studied after a 6-day period of isocaloric diet with 100% calorie requirement, of which 55% carbohydrate, 15% protein, and 30% fat) the same isocaloric diet supplemented with 3g/kg body weight/day fructose hypercaloric high fat diet with 130% energy requirement, of which 55% carbohydrate, 15% protein, 60% fat hypercaloric high fat+protein diet with 145% energy requirement, of which 55% carbohydrate, 30% protein, 60% fat Measurements performed after 6 days on each diet include intrahepatic and intramyocellular lipids (1H-MRS) hepatic and whole body insulin sensitivity (hyperinsulinemic-euglycemic clamp) body weight plasma concentrations of hormones and substrates gene expression profile in skeletal muscle (vastus lateralis) and adipose tissue (subcutaneous abdominal)

fructose, dietary lipids, dietary proteins, hepatic steatosis, insulin resistance, Healthy humans, overweight humans, obese humans

Effect of diet intervention "high fructose" in healthy non-obese offsprings of patients with type 2 diabetes

Inclusion Criteria: Males and females Age 18-40 Informed consent obtained Subgroup with overweight (body mass index [BMI] > 25) Subgroup with family history of type 2 diabetes mellitus Exclusion Criteria: Smokers Alcohol intake > 30g/day Drug abuse Diabetes mellitus Any concurrent medication Having a pacemaker History of orthopedic surgery History of metal foreign bodies

Bortolotti M, Kreis R, Debard C, Cariou B, Faeh D, Chetiveaux M, Ith M, Vermathen P, Stefanoni N, Le KA, Schneiter P, Krempf M, Vidal H, Boesch C, Tappy L. High protein intake reduces intrahepatocellular lipid deposition in humans. Am J Clin Nutr. 2009 Oct;90(4):1002-10. doi: 10.3945/ajcn.2008.27296. Epub 2009 Aug 26.

Le KA, Ith M, Kreis R, Faeh D, Bortolotti M, Tran C, Boesch C, Tappy L. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J Clin Nutr. 2009 Jun;89(6):1760-5. doi: 10.3945/ajcn.2008.27336. Epub 2009 Apr 29.