REDD1 deficiency protects against nonalcoholic hepatic steatosis induced by high‐fat diet
- Creators
- Dumas, Karine
- Ayachi, Chaima
- Gilleron, Jérôme
- Lacas-Gervais, Sandra
- Pastor, Faustine
- Favier, François Bertrand
- Peraldi, Pascal
- Vaillant, Nathalie
- Yvan‐charvet, Laurent
- Bonnafous, Stéphanie
- Patouraux, Stéphanie
- Anty, Rodolphe
- Tran, Albert
- Gual, Philippe
- Cormont, Mireille
- Tanti, Jean‐françois
- Giorgetti‐peraldi, Sophie
- Others:
- Université Côte d'Azur, Inserm, Centre Méditerranéen de Médecine Moléculaire (C3M), Team "Cellular and Molecular Pathophysiology of Obesity and Diabetes"
- Université Côte d'Azur, Centre Commun de Microscopie Appliquée (CCMA)
- Dynamique Musculaire et Métabolisme (DMEM) ; Université de Montpellier (UM)-Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE)
- Institut de Biologie Valrose (IBV) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Université Côte d'Azur (UCA)
- Université Côte d'Azur, Inserm, Centre Méditerranéen de Médecine Moléculaire (C3M), Team "Haematometabolism in Diseases"
- Université Côte d'Azur, Inserm, Centre Méditerranéen de Médecine Moléculaire (C3M), Team "Chronic Liver Diseases Associated with Steatosis"
- Fédération d'Hépatologie ; Centre Hospitalier Universitaire de Nice (CHU Nice)
- ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
- ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011)
Description
Nonalcoholic fatty liver disease is a chronic liver disease which is associated with obesity and insulin resistance. We investigated the implication of REDD1 (Regulated in development and DNA damage response-1), a stress-induced protein in the development of hepatic steatosis. REDD1 expression was increased in the liver of obese mice and morbidly obese patients, and its expression correlated with hepatic steatosis and insulin resistance in obese patients. REDD1 deficiency protected mice from the development of hepatic steatosis induced by high-fat diet (HFD) without affecting body weight gain and glucose intolerance. This protection was associated with a decrease in the expression of lipogenic genes, SREBP1c, FASN, and SCD-1 in liver of HFD-fed REDD1-KO mice. Healthy mitochondria are crucial for the adequate control of lipid metabolism and failure to remove damaged mitochondria is correlated with liver steatosis. Expression of markers of autophagy and mitophagy, Beclin, LC3-II, Parkin, BNIP3L, was enhanced in liver of HFD-fed REDD1-KO mice. The number of mitochondria showing colocalization between LAMP2 and AIF was increased in liver of HFD-fed REDD1-KO mice. Moreover, mitochondria in liver of REDD1-KO mice were smaller than in WT. These results are correlated with an increase in PGC-1α and CPT-1 expression, involved in fatty acid oxidation. In conclusion, loss of REDD1 protects mice from the development of hepatic steatosis.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-02525977
- URN
- urn:oai:HAL:hal-02525977v1
- Origin repository
- UNICA