Dietary protein diet prevents high fat induced intestinal adaptation and thereby increases intestinal lipid uptake rates in mice

Abstract

High saturated fat (HF) diets lead to obesity and an associated adaptation in the small intestine (SI), reflected by increased lipid uptake in the middle and distal part. We previously showed that a high protein (HP) diet prevents and reverses obesity and fatty liver even in the context of a HF diet. Our aim was to study if a HP diet can prevent obesogenic adaptation of the SI and consequently affect lipid handling by regional differences in gene expression.Male C57BL/6 mice were fed either a high fat, normal protein (HF‐NP) or a HF‐HP diet for 1 week. After an overnight fast mice received a lipid load containing radio labeled fatty acid (FA) and triglyceride (TG). Appearance of labels in blood was followed over 5 hours. Changes in gene expression in SI were studied using microarray and subsequent gene set enrichment analysis.The HF‐HP diet increased appearance rate of TG (35%, p=0.0407) and FA (29%, p=0.1085) in blood. Transcriptional changes were detected in the metabolism of amino acids along the SI while lipid processing and transport only increased in the proximal part of the SI.Despite a more rapid appearance of lipids in the blood, mice fed the HF‐HP diet do not develop obesity and fatty liver. This suggests that during the HP diet lipids are taken up in the proximal part of the SI and HF diet induced uptake in the lower parts is prevented.This research was supported by a FP7 Marie Curie ERG and by the Dutch Dairy Organisation (NZO).Grant Funding Source: FP7 Marie Curie ERG and by the Dutch Dairy Organisation