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Peroxisome proliferator-activated receptor gamma (PPAR?) 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 receptor? (PPAR?) is a key player in carbohydrate metabolism. While the intestine is essential for carbohydrate digestion and absorption, the role of PPAR? in enterocyte metabolic functions has been poorly investigated. This study aims at characterizing PPAR? target genes involved in intestinal metabolic functions. In microarray analysis, the LCT gene was the most upregulated by PPAR? agonists in Caco-2 cells. We confirmed that PPAR? 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 PPAR? was identified in the promoter of the human LCT gene. PPAR? modulation was able to improve symptoms induced by lactose-enriched diet in weaned rats. Our results demonstrate that PPAR? regulates LCT expression, and suggest that modulating intestinal PPAR? activity might constitute a new therapeutic strategy for lactose malabsorption.

SUBMITTER: Fumery M

PROVIDER: S-EPMC5666307 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Fumery Mathurin M Speca Silvia S Langlois Audrey A Davila Anne-Marie AM Dubuquoy Caroline C Grauso Marta M Martin Mena Anthony A Figeac Martin M Metzger Daniel D Rousseaux Christel C Colombel Jean-Frederic JF Dubuquoy Laurent L Desreumaux Pierre P Bertin Benjamin B

EMBO molecular medicine 20171101 11

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 PPA ...[more]

PMID: 28947679

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Project description:Ascites (serous fluid accumulation in the abdominal cavity) has been observed worldwide in fast growing broilers. Pulmonary vascular remodeling is an important pathological feature of broiler ascites syndrome. Peroxisome proliferators-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) are expressed in pulmonary vascular endothelial cells and vascular smooth muscle cells (VSMC) where they participate in the regulation of normal pulmonary vascular function. The objective of the present study was to investigate the effects of omega-3 fatty acids (found in fish oil) and pioglitazone (PIO) as natural and synthetic PPARγ ligands supplementation on PPARγ and PGC-1α expression in the prevention of pulmonary arterial hypertension (PAH) syndrome in broiler chickens. The experiment was conducted with 4 treatment groups: 1) negative control, normal temperature conditions with basal diet; 2) positive control, low-temperature conditions with basal diet; 3) positive control + 10 mg PIO/kg of weight/d and 4) positive control + 1% FO. Each treatment had 5 replicates. Ascites heart index (RV/TV) was significantly (P < 0.05) reduced in chickens receiving FO (0.20) and PIO (0.21) compared to the positive control group (0.26). The addition of PIO in broilers under cold-induced ascites significantly increased the expression of PPARγ (9.44) and PGC-1α (5.81) genes in lung tissue compared to the negative control group (1.03, P < 0.05). Proliferative indexes of VSMC in pulmonary arteries such as PMT, PIT, and percentage wall thickness were significantly elevated in positive control group, indicating that pulmonary vascular remodeling occurred following VSMC proliferation in ascites. The vessel internal diameter was increased in FO and PIO groups. Based on these results, activation and expression of PPARγ and PGC-1α genes as a critical regulator of pulmonary artery smooth muscle cell using ligands, especially PIO, can be effective in reducing the incidence of PAH in broiler chickens.

Dataset Information

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

Publications

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

Similar Datasets

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