• plasma triglycerides and free fatty acids [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  
• intra-hepatic lipids [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  
• insulin sensitivity [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  

• lipid oxidation [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  
• plasma beta-hydroxybutyrate [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  
• gene expression in skeletal muscle and adipose tissue [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  

Other: changes in energy and macronutrient intake
hypercaloric diet fructose supplementation fat supplementation protein supplementation

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)