REDD1 deficiency protects against nonalcoholic hepatic steatosis induced by high-fat diet.
Adult
Animals
Autophagy
Carnitine O-Palmitoyltransferase
/ genetics
Cells, Cultured
Diet, High-Fat
/ adverse effects
Fatty Acid Synthase, Type I
/ genetics
Female
Gene Deletion
Humans
Male
Mice
Mitophagy
Non-alcoholic Fatty Liver Disease
/ etiology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ genetics
Stearoyl-CoA Desaturase
/ genetics
Sterol Regulatory Element Binding Protein 1
/ genetics
Transcription Factors
/ deficiency
REDD1
autophagy
hepatic steatosis
obesity
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
17
07
2019
revised:
24
01
2020
accepted:
24
01
2020
pubmed:
12
2
2020
medline:
20
1
2021
entrez:
12
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32043636
doi: 10.1096/fj.201901799RR
doi:
Substances chimiques
Ddit4 protein, mouse
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Srebf1 protein, mouse
0
Sterol Regulatory Element Binding Protein 1
0
Transcription Factors
0
Scd1 protein, mouse
EC 1.14.19.1
Stearoyl-CoA Desaturase
EC 1.14.19.1
Carnitine O-Palmitoyltransferase
EC 2.3.1.21
Fasn protein, mouse
EC 2.3.1.85
Fatty Acid Synthase, Type I
EC 2.3.1.85
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5046-5060Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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