Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut

Autor: Fumery, Mathurin, Speca, Silvia, Langlois, Audrey, Davila, Anne‐Marie, Dubuquoy, Caroline, Grauso, Marta, Martin Mena, Martin, Figeac, Martin, Metzger, Daniel, Rousseaux, Christel, Colombel, Jean‐Frederic, Dubuquoy, Laurent, Desreumaux, Pierre, Bertin, Benjamin
Přispěvatelé: Lille Inflammation Research International Center (LIRIC), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, Intestinal Biotech Development, Université Lille 2 - Faculté de Médecine, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Hôpital Claude Huriez [Lille], CHU Lille, DigestScience Foundation, Institut National de la Sante et de la Recherche (Inserm), Societe Nationale Franaise de Gastro-Entdrologie (FARE), NograPharma Ltd, Dublin, Faculté de Médecine Henri Warembourg - Université de Lille
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: EMBO Molecular Medicine
EMBO Molecular Medicine, Wiley Open Access, 2017, 9 (11), pp.1471-1481. ⟨10.15252/emmm.201707795⟩
EMBO Molecular Medicine, 2017, 9 (11), pp.1471-1481. ⟨10.15252/emmm.201707795⟩
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201707795⟩
Popis: International audience; Lactase (LCT) deficiency affects approximately 75% of the world's adult population and may lead to lactose malabsorption and intolerance. Currently, the regulation of LCT gene expression remains poorly known. Peroxisome proliferator activator receptorγ (PPARγ) is a key player in carbohydrate metabolism. While the intestine is essential for carbohydrate digestion and absorption, the role of PPARγ in enterocyte metabolic functions has been poorly investigated. This study aims at characterizing PPARγ target genes involved in intestinal metabolic functions. In microarray analysis, the LCT gene was the most upregulated by PPARγ agonists in Caco‐2 cells. We confirmed that PPARγ agonists were able to increase the expression and activity of LCT both in vitro and in vivo in the proximal small bowel of rodents. The functional response element activated by PPARγ was identified in the promoter of the human LCT gene. PPARγ modulation was able to improve symptoms induced by lactose‐enriched diet in weaned rats. Our results demonstrate that PPARγ regulates LCT expression, and suggest that modulating intestinal PPARγ activity might constitute a new therapeutic strategy for lactose malabsorption.
Databáze: OpenAIRE
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