title: Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet.
abstract: 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.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMR S 872, INSERM, U 872, Paris, France.
authors.forename: Sandra Jimena
authors.initials: SJ
authors.lastname: Hernández Vallejo
authors.forename: Malik
authors.initials: M
authors.lastname: Alqub
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.forename: Céline
authors.initials: C
authors.lastname: Cruciani-Guglielmacci
authors.forename: Philippe
authors.initials: P
authors.lastname: Delerive
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: Athina-Despina
authors.initials: AD
authors.lastname: Kalopissis
authors.forename: Jean
authors.initials: J
authors.lastname: Chambaz
authors.forename: Monique
authors.initials: M
authors.lastname: Rousset
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lacorte
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D019518:Postprandial Period / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015430:Weight Gain
chemical_list: D004268:DNA-Binding Proteins; D004041:Dietary Fats; D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1