Effects of High-fat and Low-fat Diet on the Gut

Rationale: The prevalence of the metabolic syndrome is strongly increasing in developed countries. The role of the small intestine seems important in the development of the metabolic syndrome. Although it is known that a high-fat Western-style of diet has deleterious effects on (post-prandial) lipidemia and glucose homeostases, effects of such a diet on the small intestine is not known. To elucidate the role of the small intestine on the early development of the metabolic syndrome, the effects of a high-fat (HF) and a low-fat (LF) diet will be examined on gene expression in the small intestine and early biomarkers in blood of healthy subjects. Objective: The objective of this study is to compare in healthy subjects the effects of a HF diet (40 En% fat) with those of a LF diet (20 En% fat) on early biomarkers and parameters of metabolic stress in blood and on expression of genes in the small intestine. Additional research objectives are: * To compare the diet-induced changes in transcriptome profile of the small intestine with more easily accessible peripheral blood mononuclear cells (PBMC) * To establish effects of HF and LF diet on basal gut permeability and after a chenodeoxycholic acid (CDCA) load (second hit). Study design: Randomised crossover design. The duration of the experimental periods (HF and LF diet) will be 28 days, separated by a wash out period of at least 3 weeks. At day 21 of each intervention period a postprandial test will be performed and duodenum biopsies will be taken. At day 25 and 28 of each intervention period, respectively, basal gut permeability and gut permeability after a CDCA load will be determined with a sugar recovery test. Study population: Ten healthy men in the age of 18-60 years, without a history of any gastrointestinal disorders or complaints. Intervention: Subjects will consume in random order: * a HF diet (40 En% fat, 45 En% carbohydrates and 15 En% proteins) * a LF diet (20 En% fat, 65 En% carbohydrates and 15 En% pr