Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse

Valerie Petit,Laurent Arnould,Pascal Martin,Marie-Claude Monnot,Thierry Pineau,Philippe Besnard,Isabelle Niot

doi:10.1194/jlr.m600283-jlr200

Abstract

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. It is unknown whether a fat-mediated adaptation to lipid absorption takes place. To address this issue, mice fed a high-fat diet (40%, w/w) were refed or not a control diet (3%, w/w) for 3 additive weeks. Despite daily lipid intake 7.7-fold higher than in controls, fecal lipid output remained unchanged in mice fed the triglyceride (TG)-rich diet. In situ isolated jejunal loops revealed greater [1-(14)C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity. Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III). These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse.

Highlights

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive
The intestinal functions of most lipid binding protein (LBP) remain elusive, it can be hypothesized that a high fat supply triggers a coordinated change in LBP expression, increasing intestinal absorption capacity
Dietary lipids being the strongest stimulators of mucosal regeneration [8]. These observations strongly suggest that the high TG bioavailability of gut might not be attributable to inborn properties but to acquired properties. To determine whether such a lipid-mediated adaptation exists, a chronic high-fat diet effect on absorption capacity of the small intestine was studied in mice

Summary

Introduction

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. In situ isolated jejunal loops revealed greater [1-14C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III) These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse.—Petit, V., L. These observations strongly suggest that the high TG bioavailability of gut might not be attributable to inborn properties but to acquired properties To determine whether such a lipid-mediated adaptation exists, a chronic high-fat diet effect on absorption capacity of the small intestine was studied in mice. They provide evidence that the small intestine plays an active role in the regulation of triglyceridemia, especially during the postprandial state

Methods

Results

Conclusion