Abstract
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.
Highlights
Lactase (LCT) deficiency affects approximately 75% of the world’s adult population and may lead to lactose malabsorption and intolerance
Gene expression profiles of the Caco-2 intestinal epithelial cell line stimulated by Peroxisome proliferator activator receptorc (PPARc) agonists were first assessed by microarray analysis
In order to strengthen these results, we evaluated the ability of two other PPARc agonists to increase LCT expression: rosiglitazone (Rosi, 1 lM), another TZD drug class ligand, and the trans-10, cis12-conjugated linoleic acid (CLA, 1 mM) isomer, a natural PPARc modulator
Summary
Lactase (LCT) deficiency affects approximately 75% of the world’s adult population and may lead to lactose malabsorption and intolerance. The regulation of LCT gene expression remains poorly known. While the intestine is essential for carbohydrate digestion and absorption, the role of PPARc in enterocyte metabolic functions has been poorly investigated. This study aims at characterizing PPARc target genes involved in intestinal metabolic functions. The LCT gene was the most upregulated by PPARc agonists in Caco-2 cells. We confirmed that PPARc 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 PPARc was identified in the promoter of the human LCT gene. Our results demonstrate that PPARc regulates LCT expression, and suggest that modulating intestinal PPARc activity might constitute a new therapeutic strategy for lactose malabsorption
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