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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/G782    most recent 90324.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hernández Vallejo, S. J. Articles by Lacorte, J.-M. Search for Related Content PubMed PubMed Citation Articles by Hernández Vallejo, S. J. Articles by Lacorte, J.-M.

MUCOSAL BIOLOGY

Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet

¹Université Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris; ²INSERM, U 872, Paris; ³Université Paris Descartes, UMR S 872, Paris; ⁴Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, Les Ulis; ⁵Université Paris-VII, CNRS UMR 7059, Paris; and ⁶Clermont Université; UMR CNRS6247; CRNH-Auvergne, Aubière, France

Submitted 5 May 2008 ; accepted in final form 29 January 2009

Western diet is characterized by a hypercaloric and hyperlipidic intake, enriched in saturated fats, that is associated with the increased occurrence of metabolic diseases. To cope with this overload of dietary lipids, the intestine, which delivers dietary lipids to the body, has to adapt its capacity in lipid absorption and lipoprotein synthesis. We have studied the early effects of a high-fat diet (HFD) on intestinal lipid metabolism in mice. After 7 days of HFD, mice displayed normal fasting triglyceridemia but postprandial hypertriglyceridemia. HFD induced a decreased number of secreted chylomicrons with increased associated triglycerides. Secretion of larger chylomicrons was correlated with increased intestinal microsomal triglyceride transfer protein (MTP) content and activity. Seven days of HFD induced a repression of genes involved in fatty acid synthesis (FAS, ACC) and an increased expression of genes involved in lipoprotein assembly (apoB, MTP, and apoA-IV), suggesting a coordinated control of intestinal lipid metabolism to manage a high-fat loading. Of note, the mature form of the transcription factor SREBP-1c was increased and translocated to the nucleus, suggesting that it could be involved in the coordinated control of gene transcription. Activation of SREBP-1c was partly independent of LXR. Moreover, HFD induced hepatic insulin resistance whereas intestine remained insulin sensitive. Altogether, these results demonstrate that a short-term HFD is sufficient to impact intestinal lipid metabolism, which might participate in the development of dyslipidemia and metabolic diseases.

enterocyte; chylomicron; lipid metabolism; SREBP-1C