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Journal of Lipid Research, Vol. 48, 278-287, February 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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^* and Isabelle Niot^1,*

^* Physiologie de la Nutrition, Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation, Unité Mixte de Recherche Centre Europeen des Sciences du Gout 5170-Centre National de la Recherche Scientifique/1214 Institut National de la Recherche Agronomique/Université de Bourgogne, Dijon; France
Department of Pathology, Centre G-F Leclerc, Dijon, France
Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique, Toulouse, France

Published, JLR Papers in Press, November 18, 2006.

¹ To whom correspondence should be addressed: e-mail: niot{at}u-bourgogne.fr

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 [1-¹⁴C]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. 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.

Supplementary key words small intestine • intestinal proliferation • lipid binding proteins • triglyceridemia

Abbreviations: apoA-IV, apolipoprotein A-IV; FAT/CD36, fatty acid transporter; FATP-4, fatty acid transport protein 4; I-FABP, intestinal fatty acid binding protein; LBP, lipid binding protein; LCFA, long-chain fatty acid; L-FABP, liver fatty acid binding protein; LPL, lipoprotein lipase; MTP, microsomal triglyceride transfer protein; PPAR, peroxisome proliferator-activated receptor; TG, triglyceride

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