Dietary Treatment Study of Fat Synthesis and Risk of Cardiovascular Disease

The purpose of this study is to find out how the amount of fat or sugar in a person's diet, or the number of meals eaten each day, affect the amount of fat that people's bodies make, the types of fats in the bloodstream, and how much fat is stored in the liver. The study is funded by the National Institutes of Health.

The study consists of two 10-day feeding periods that are separated by approximately two weeks. During each feeding period all food and beverages to be consumed will be provided by the study. In Study 1, participants will be randomly assigned to receive one of two diets. Both diets are designed to maintain weight at a constant level. The diets are balanced nutritionally and have the same amount of protein. One diet has higher amounts of sugar, while the other has higher amounts of fat. For one 10-day period, the diet will be fed as two large meals ('meal-feeding'). For the other 10-day period, the identical diet will be fed as 8 small meals ('nibbling'). Half of the participants will meal-feed first, while the other half will 'nibble' first. The order of nibbling or meal feeding will be determined randomly. In Study 2, the number of meals eaten per day will remain fixed at three (no nibbling or meal feeding). Participants will receive both the diet higher in sugar and the diet higher in fat. However, they will be randomly assigned to start one followed by the other for each 10-day feeding period. At the end of each 10-day feeding period, participants will spend two nights in a research ward (Clinical Research Center) to undergo testing.

Differences between high carbohydrate and high fat diets on postprandial de novo lipogenesis De novo lipogenesis will be measured using stable (not radioactive) isotopes given intravenously and orally during feeding.

Differences between consuming the same diet as eight small meals per day or two larger meals per day on postprandial de novo lipogenesis. Please see description of measurement of de novo lipogenesis under aim 1.

Effects of diet composition or meal frequency on fat stored in the liver. Liver fat content will be measured non-invasively using magnetic resonance spectroscopy.

Effects of diet composition or meal frequency on the types of fats in the bloodstream that might affect risk of heart disease. The types of fats in the bloodstream will be measured in blood samples collected while the participant is fasting and also during the stable isotope/feeding study of de novo lipogenesis.

Inclusion Criteria: overweight or obese men and women ages 20-65 years Exclusion Criteria: pregnancy or lactation within the past six months type 1 or 2 diabetes mellitus] AST and ALT above upper limit of normal (ULN) fasting triglyceride or total cholesterol levels >ULN Hgb below the lower of limit of normal positive HIV antibody test or hepatitis serologies use of any antidiabetic medications or lipid-lowering drugs history of surgery for obesity change in body weight >5% within preceding 6 months (self report) claustrophobia, presence of metal implants weight over 350 lbs