Short-Term Adaptation of Postprandial Lipoprotein Secretion and Intestinal ‎Gene Expression to a High-Fat Diet

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Journal Title, Volume, Page: 
Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G782-92.
Year of Publication: 
2009
Authors: 
Malik Alqub
Universite Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris
Current Affiliation: 
Faculty of Medicine & Health Sciences, Department of Biomedical Sciences, An-Najah National University, Nablus, Palestine
Hernández Vallejo SJ
Universite Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris
Serge Luquet
Universite Paris-VII, CNRS UMR 7059, Paris
Cruciani-Guglielmacci C
Universite Paris-VII, CNRS UMR 7059, Paris
Delerive P
Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, Les Ulis
Lobaccaro JM
Clermont Universite; UMR CNRS6247; CRNH-Auvergne, Aubiere, France
Kalopissis AD
Universite Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris
Chambaz J
Universite Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris
Rousset M
Universite Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris
Lacorte JM
Universite Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris
Preferred Abstract (Original): 

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.

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