Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis
| Autor: | Maurice M.A.L. Pelsers, Marie Claude Monnot, Jan F. C. Glatz, Pascal Degrace, Fatiha Nassir, Valérie Petit, Philippe Besnard, Lionel C. Clement, Nada A. Abumrad, Hélène Poirier, Isabelle Niot, Thi Thu Trang Tran |
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| Přispěvatelé: | Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Department of Medicine, University of Washington, Department of Molecular Genetics [Maastricht, The Netherlands], Maastricht University [The Netherlands], Physiopathologie des Dyslipidémies (U866, Lipides et nutrition, équipe 6), Moleculaire Genetica, Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
CD36 Antigens
Male MTP CD36 [SDV]Life Sciences [q-bio] Biochemistry Microsomal triglyceride transfer protein Mice 0302 clinical medicine Intestinal mucosa Cricetinae Chylomicrons Lipoprotein Hypertriglyceridemia Mice Knockout 0303 health sciences Mitogen-Activated Protein Kinase 3 biology Postprandial Period Lipid-binding Protein Intestine ApoB48 ERK medicine.anatomical_structure Postprandial lipids (amino acids peptides and proteins) Apolipoprotein B-48 MAP Kinase Signaling System Enterocyte CHO Cells Chylomicron 03 medical and health sciences Cricetulus parasitic diseases medicine Animals Rats Wistar Molecular Biology 030304 developmental biology Ubiquitination Lipid absorption Lipid metabolism Cell Biology Lipid Metabolism Rats Enterocytes Metabolism biology.protein [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition 030217 neurology & neurosurgery |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, 286 (28), pp.25201-25210. ⟨10.1074/jbc.M111.233551⟩ Journal of Biological Chemistry, 286(28), 25201-25210. American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M111.233551⟩ |
| Popis: | International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but only when the diet contains lipids. This drop is significant 1 h after a lipid supply and associates with ubiquitination of CD36. Using CHO cells expressing CD36, it is shown that the digestion products LCFA and diglycerides trigger CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevents the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 is shown to be required for lipid activation of ERK1/2, which associates with an increase of the key chylomicron synthesis proteins, apolipoprotein B48 and microsomal triglyceride transfer protein. Therefore, intestinal CD36, possibly through ERK1/2-mediated signaling, is involved in the adaptation of enterocyte metabolism to the postprandial lipid challenge by promoting the production of large triglyceride-rich lipoproteins that are rapidly cleared in the blood. This suggests that CD36 may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks. |
| Databáze: | OpenAIRE |
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