Abstract 128: Short-Term, High-Saturated and Trans Fatty Acid Diet Increases Expression of Key Intestinal Genes Involved in Lipoprotein Metabolism in Healthy Males

Abstract

Dietary saturated fat (SFA) and trans fatty acids (TFA) have been linked to an increased risk of cardiovascular disease mainly by increasing plasma LDL-C levels. The modulation of cholesterol and fatty acids homeostasis by SFA and TFA is thought to be mediated by changes in expression of key intestinal genes involved in lipid and lipoprotein metabolism. However, the short-term impact of dietary fat intake on expression of these genes has not been fully investigated. To test whether short-term changes in SFA and TFA intake affects expression of key intestinal genes involved in lipid and lipoprotein metabolism, we conducted a randomized, double-blind, cross-over study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: 1) high-fat diet (37% energy from fat, 15% from SFA, 3.5% from TFA and 50% energy from carbohydrate) and 2) low-fat diet (25% energy from fat, 6% from SFA, 0% from TFA and 62% energy from carbohydrate) in random order, each separated by a two-week washout period. Fasting plasma lipid levels were determined and expression of key genes involved in lipid and lipoprotein metabolism was compared by real-time PCR quantification in duodenal biopsy specimens obtained in the fasted state after 3 days of feeding on each diet. Following the 3-day high-fat diet, plasma-C (+7.4%, P=0.02), LDL-C (+16.9%, P=0.005) and HDL-C (+9.3%, P=0.002) levels were significantly increased as compared to low-fat diet. Plasma triglycerides (-31.7%, P=0.001) and apolipoprotein B-48 (-39.6%, P=0.003) levels were significantly decreased after the high-fat diet relative to the low-fat diet. The high-fat diet also resulted in significant increases in intestinal mRNA expression levels of SREBP-2, HNF-4α, PPAR-α, PPAR-γ, NPC1L1, ABCG8, FABP-2, ACAC-α, SCD-1, ELOVL5, DGAT-2, apolipoprotein B, MTTP, SAR1β and LDL receptor. These findings suggest that short-term exposure to a high-SFA and TFA diet upregulates the expression of key genes involved in lipid and lipoprotein metabolism at the enterocyte level.