Short-term, high-fat diet increases the expression of key intestinal genes involved in lipoprotein metabolism in healthy men

Abstract

The modulation of cholesterol and fatty acid homeostasis by dietary fatty acids is thought to be mediated by changes in the expression of key intestinal genes involved in lipoprotein metabolism. However, the short-term effect of dietary fat intake on the expression of these genes has not been fully investigated in humans. To test whether short-term changes in dietary fatty acid intake affect the expression of key intestinal genes involved in lipoprotein metabolism, we conducted a randomized, double-blind, crossover study in 12 nonobese, healthy men with normal plasma lipid profiles. Participants were subjected to the following 2 intensive 3-d dietary interventions under isocaloric conditions: 1) a high-fat diet (37% of energy from fat and 50% of energy from carbohydrates) and 2) a low-fat diet (25% of energy from fat and 62% of energy from carbohydrates). Expressions of key genes involved in lipoprotein metabolism were compared by using real-time polymerase chain reaction quantification on duodenal biopsy specimens obtained in a fasting state after each diet. After the 3-d high-fat diet, plasma cholesterol, LDL cholesterol, and HDL cholesterol concentrations were significantly higher than concentrations observed after the low-fat diet was consumed. The high-fat diet also resulted in significant increases in the intestinal messenger RNA expression of several key genes involved in lipoprotein metabolism. Plasma triglycerides and apolipoprotein B-48 concentrations were significantly lower after the high-fat diet than after the low-fat diet. These findings suggest that short-term exposure to a high-fat diet upregulates the expression of key genes involved in lipid and lipoprotein metabolism at the enterocyte level. This trial was registered at clinicaltrials.gov as NCT01806441.