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

Fiche publication


Date publication

septembre 2017

Journal

EMBO molecular medicine

Auteurs

Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel


Tous les auteurs :
Fumery M, Speca S, Langlois A, Davila AM, Dubuquoy C, Grauso M, Martin Mena A, Figeac M, Metzger D, Rousseaux C, Colombel JF, Dubuquoy L, Desreumaux P, Bertin B

Résumé

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.

Mots clés

PPARgamma, hypolactasia, intestinal epithelial cells, lactase, lactose intolerance

Référence

EMBO Mol Med. 2017 Sep;: