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

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.

Impact of elastin-derived VGVAPG peptide on bidirectional interaction between peroxisome proliferator-activated receptor gamma (Pparγ) and beta-galactosidase (β-Gal) expression in mouse cortical astrocytes in vitro

“…Furthermore, the functional response element activated by PPARγ was identified in the promoter of the human GLB1 gene. PPARγ was also shown to regulate β-Gal expression and activity in the gut (Fumery et al 2017). Our data show a similar relation; moreover, we suggest a bidirectional interaction between Pparγ and β-Gal.…”

“…### P < 0.001 vs. the rosiglitazone or pioglitazone treated cells and VGVAPG co-treated with rosiglitazone or pioglitazone after 48 h of using Glb1 siRNA, we observed a decrease in the expression of both the β-Gal and Pparγ protein. Similar use of Pparγ siRNA caused a decrease in the expression of both the β-Gal and Pparγ protein after 48 h. It was found that PPARγ agonists are able to induce GLB1 mRNA expression and activity in Caco-2 cells (Fumery et al 2017). Furthermore, the functional response element activated by PPARγ was identified in the promoter of the human GLB1 gene.…”

“…We observed a similar situation in our research, where in concentrations of 50 nM, 1 and 50 μM the VGVAPG peptide acted in various ways. To date, only a few papers have described that EDPs or the VGVAPG peptide increase the expression of GLB1 mRNA in normal human bronchial epithelial (16HBE) cells or colon adenocarcinoma (Caco-2) cells (Toupance et al 2012;Fumery et al 2017). Contrarily, only the available data show that there was an increase in Pparγ mRNA expression in the fat tissue of mice injected with EDPs (Blaise et al 2013).…”

Whole blood transcriptional responses of very preterm infants during late-onset sepsis

“…The sterol regulatory elementbinding proteins (SREBP) pathway, involved in responding to low concentrations of cholesterol and subsequent promotion of cholesterol biosynthesis [37,38], was over-represented along with significant up-regulation of cholesterol biosynthesis genes SREBF2, DHCR7, INSIG1, ERLIN2, SQLE, IDI1 and LDLR (Fig 3, Table 2 and S5 Table). Immune-metabolic regulatory genes, PPARG (encoding the proliferator-activated receptor gamma protein, a nuclear receptor involved in controlling beta-oxidation of fatty acids and regulation of glucose metabolism) [39,40] and CEBPB (a transcription factor important for regulating immune and inflammatory response genes) were also up-regulated. Importantly, this metabolism sub-network indicated connections between cholesterol biosynthesis genes (i.e.…”

In Vitro Human Cell–Based Experimental Models for the Evaluation of Enteric Metabolism and Drug Interaction Potential of Drugs and Natural Products

“…Peroxisome proliferator-activated receptors (PPARs): The three major PPARs are PPARa, PPARb/d, and PPARg [nuclear receptor subfamily 1, group C, members 1, -2, and -3, respectively]. In humans, PPARa is present mainly in liver, heart, and kidney; PPARb/d is in all organs evaluated including intestine (Peters et al, 2019); and PPARg in adipose tissue, large intestine, macrophages, monocytes, and Caco-2 cells (Dubuquoy et al, 2006;Couvigny et al, 2015;Fumery et al, 2017). Intestinal microbiota play key roles in intestinal inflammation via the production of PPAR agonists and antagonists, suggesting that PPAR may be involved in the pathophysiology of intestinal inflammatory diseases such as irritable bowel syndrome (Belmonte et al, 2012).…”