Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production
| Autor: | Anne Tailleux, Véronique Touche, Rémy Hanf, Olivier Briand, Sophie Colin, Sophie Lestavel, Morgane Baron, Kristiaan Wouters, François Pattou, Bart Staels, Giulia Chinetti |
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| Přispěvatelé: | Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de chirurgie générale et endocrinienne, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Thérapie cellulaire du diabète, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Genfit, Entreprise biopharmaceutique GENFIT Loos, This work was supported by grants from Université Lille 2, Région Nord/Pas-de-Calais, the FEDER and the 'Fondation Leducq'., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Derudas, Marie-Hélène |
| Rok vydání: | 2012 |
| Předmět: |
Apolipoprotein B
Peroxisome proliferator-activated receptor MESH: Butyrates 030204 cardiovascular system & hematology PPARα MESH: Lipoproteins HDL MESH: Mice Knockout chemistry.chemical_compound MESH: Enterocytes Mice 0302 clinical medicine High-density lipoprotein Chalcones MESH: Phenylurea Compounds MESH: Animals MESH: Propionates MESH: PPAR alpha Cells Cultured chemistry.chemical_classification Mice Knockout 0303 health sciences Fenofibrate biology Fatty Acids MESH: Apolipoproteins B MESH: Fatty Acids Butyrates Jejunum lipids (amino acids peptides and proteins) Female Peroxisome proliferator-activated receptor alpha MESH: Caco-2 Cells Cardiology and Cardiovascular Medicine Lipoproteins HDL medicine.drug MESH: Cells Cultured MESH: Esterification medicine.medical_specialty HDL Article 03 medical and health sciences Internal medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology medicine Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology PPAR alpha intestine MESH: Mice MESH: Chalcones 030304 developmental biology Apolipoproteins B MESH: Humans Esterification Cholesterol business.industry Phenylurea Compounds dyslipidemia Lipid metabolism Endocrinology Enterocytes chemistry MESH: Jejunum biology.protein Caco-2 Cells Propionates business MESH: Female Chylomicron |
| Zdroj: | European Heart Journal European Heart Journal, 2013, 34 (32), pp.2566-74. ⟨10.1093/eurheartj/ehs227⟩ European Heart Journal, Oxford University Press (OUP): Policy B, 2013, 34 (32), pp.2566-74. ⟨10.1093/eurheartj/ehs227⟩ |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehs227⟩ |
| Popis: | International audience; AIMS: Peroxisome proliferator-activated receptor (PPAR)-α is a transcription factor controlling lipid metabolism in liver, heart, muscle, and macrophages. Peroxisome proliferator-activated receptor-α activation increases plasma HDL cholesterol and exerts hypotriglyceridaemic actions via the liver. However, the intestine expresses PPAR-α, produces HDL and chylomicrons, and is exposed to diet-derived PPAR-α ligands. Therefore, we examined the effects of PPAR-α activation on intestinal lipid and lipoprotein metabolism. METHODS AND RESULTS: The impact of PPAR-α activation was evaluated in term of HDL-related gene expression in mice, ex vivo in human jejunal biopsies and in Caco-2/TC7 cells. Apolipoprotein-AI/HDL secretion, cholesterol esterification, and trafficking were also studied in vitro. In parallel to improving plasma lipid profiles and increasing liver and intestinal expression of fatty acid oxidation genes, treatment with the dual PPAR-α/δ ligand GFT505 resulted in a more pronounced increase in plasma HDL compared with fenofibrate in mice. GFT505, but not fenofibrate, increased the expression of HDL production genes such as apolipoprotein-AI and ATP-binding cassette A1 transporter in murine intestines. A similar increase was observed upon PPAR-α activation of human biopsies and Caco-2/TC7 cells. Additionally, HDL secretion by Caco-2/TC7 cells increased. Moreover, PPAR-α activation decreased the cholesterol esterification capacity of Caco-2/TC7 cells, modified cholesterol trafficking, and reduced apolipoprotein-B secretion. CONCLUSION: Peroxisome proliferator-activated receptor-α activation reduces cholesterol esterification, suppresses chylomicron, and increases HDL secretion by enterocytes. These results identify the intestine as a target organ of PPAR-α ligands with entero-hepatic tropism to reduce atherogenic dyslipidaemia. |
| Databáze: | OpenAIRE |
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