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 carboh...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-09-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201707795 |
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| author | Mathurin Fumery Silvia Speca Audrey Langlois Anne‐Marie Davila Caroline Dubuquoy Marta Grauso Anthony Martin Mena Martin Figeac Daniel Metzger Christel Rousseaux Jean‐Frederic Colombel Laurent Dubuquoy Pierre Desreumaux Benjamin Bertin |
| author_facet | Mathurin Fumery Silvia Speca Audrey Langlois Anne‐Marie Davila Caroline Dubuquoy Marta Grauso Anthony Martin Mena Martin Figeac Daniel Metzger Christel Rousseaux Jean‐Frederic Colombel Laurent Dubuquoy Pierre Desreumaux Benjamin Bertin |
| author_sort | Mathurin Fumery |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-41d9acc15de04a65b09a64e46554e7da |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2017-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-41d9acc15de04a65b09a64e46554e7da2025-08-20T03:42:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-09-019111471148110.15252/emmm.201707795Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gutMathurin Fumery0Silvia Speca1Audrey Langlois2Anne‐Marie Davila3Caroline Dubuquoy4Marta Grauso5Anthony Martin Mena6Martin Figeac7Daniel Metzger8Christel Rousseaux9Jean‐Frederic Colombel10Laurent Dubuquoy11Pierre Desreumaux12Benjamin Bertin13U995—LIRIC—Lille Inflammation Research International Center, Univ. LilleU995—LIRIC—Lille Inflammation Research International Center, Univ. LilleU995—LIRIC—Lille Inflammation Research International Center, Univ. LilleUMR0914, Institut National de la Recherche Agronomique/AgroParisTech, Université Paris‐SaclayIntestinal Biotech DevelopmentUMR0914, Institut National de la Recherche Agronomique/AgroParisTech, Université Paris‐SaclayU995—LIRIC—Lille Inflammation Research International Center, Univ. LilleFunctional and Structural Genomic Platform, Université de LilleInstitut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, UMR7104/INSERM U964/Université de Strasbourg, Collège de FranceIntestinal Biotech DevelopmentThe Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount SinaiU995—LIRIC—Lille Inflammation Research International Center, Univ. LilleU995—LIRIC—Lille Inflammation Research International Center, Univ. LilleU995—LIRIC—Lille Inflammation Research International Center, Univ. LilleAbstract 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.https://doi.org/10.15252/emmm.201707795hypolactasiaintestinal epithelial cellslactaselactose intolerancePPARgamma |
| spellingShingle | Mathurin Fumery Silvia Speca Audrey Langlois Anne‐Marie Davila Caroline Dubuquoy Marta Grauso Anthony Martin Mena Martin Figeac Daniel Metzger Christel Rousseaux Jean‐Frederic Colombel Laurent Dubuquoy Pierre Desreumaux Benjamin Bertin Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut EMBO Molecular Medicine hypolactasia intestinal epithelial cells lactase lactose intolerance PPARgamma |
| title | Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut |
| title_full | Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut |
| title_fullStr | Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut |
| title_full_unstemmed | Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut |
| title_short | Peroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut |
| title_sort | peroxisome proliferator activated receptor gamma pparγ regulates lactase expression and activity in the gut |
| topic | hypolactasia intestinal epithelial cells lactase lactose intolerance PPARgamma |
| url | https://doi.org/10.15252/emmm.201707795 |
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