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Publication : Peroxisome proliferator-activated receptor gamma (PPAR?) regulates lactase expression and activity in the gut.

First Author  Fumery M Year  2017
Journal  EMBO Mol Med Volume  9
Issue  11 Pages  1471-1481
PubMed ID  28947679 Mgi Jnum  J:268571
Mgi Id  MGI:6161924 Doi  10.15252/emmm.201707795
Citation  Fumery M, et al. (2017) Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates lactase expression and activity in the gut. EMBO Mol Med 9(11):1471-1481
abstractText  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 receptorgamma (PPARgamma) is a key player in carbohydrate metabolism. While the intestine is essential for carbohydrate digestion and absorption, the role of PPARgamma in enterocyte metabolic functions has been poorly investigated. This study aims at characterizing PPARgamma target genes involved in intestinal metabolic functions. In microarray analysis, the LCT gene was the most upregulated by PPARgamma agonists in Caco-2 cells. We confirmed that PPARgamma 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 PPARgamma was identified in the promoter of the human LCT gene. PPARgamma modulation was able to improve symptoms induced by lactose-enriched diet in weaned rats. Our results demonstrate that PPARgamma regulates LCT expression, and suggest that modulating intestinal PPARgamma activity might constitute a new therapeutic strategy for lactose malabsorption.
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