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Ablation of catalase promotes non-alcoholic fatty liver via oxidative stress and mitochondrial dysfunction in diet-induced obese mice.

Authors :
Shin, Su-Kyung
Cho, Hyun-Woo
Song, Seung-Eun
Bae, Jae-Hoon
Im, Seung-Soon
Hwang, Inha
Ha, Hunjoo
Song, Dae-Kyu
Source :
Pflügers Archiv: European Journal of Physiology; Jun2019, Vol. 471 Issue 6, p829-843, 15p
Publication Year :
2019

Abstract

Hydrogen peroxide (H<subscript>2</subscript>O<subscript>2</subscript>) produced endogenously can cause mitochondrial dysfunction and metabolic complications in various cell types by inducing oxidative stress. In the liver, oxidative and endoplasmic reticulum (ER) stress affects the development of non-alcoholic fatty liver disease (NAFLD). Although a link between both stresses and fatty liver diseases has been suggested, few studies have investigated the involvement of catalase in fatty liver pathogenesis. We examined whether catalase is associated with NAFLD, using catalase knockout (CKO) mice and the catalase-deficient human hepatoma cell line HepG2. Hepatic morphology analysis revealed that the fat accumulation was more prominent in high-fat diet (HFD) CKO mice compared to that in age-matched wild-type (WT) mice, and lipid peroxidation and H<subscript>2</subscript>O<subscript>2</subscript> release were significantly elevated in CKO mice. Transmission electron micrographs indicated that the liver mitochondria from CKO mice tended to be more severely damaged than those in WT mice. Likewise, mitochondrial DNA copy number and cellular ATP concentrations were significantly lower in CKO mice. In fatty acid-treated HepG2 cells, knockdown of catalase accelerated cellular lipid accumulation and depressed mitochondrial biogenesis, which was recovered by co-treatment with N-acetyl cysteine or melatonin. This effect of antioxidant was also true in HFD-fed CKO mice, suppressing fatty liver development and improving hepatic mitochondrial function. Expression of ER stress marker proteins and hepatic fat deposition also increased in normal-diet, aged CKO mice compared to WT mice. These findings suggest that H<subscript>2</subscript>O<subscript>2</subscript> production may be an important event triggering NAFLD and that catalase may be an attractive therapeutic target for preventing NAFLD. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00316768
Volume :
471
Issue :
6
Database :
Complementary Index
Journal :
Pflügers Archiv: European Journal of Physiology
Publication Type :
Academic Journal
Accession number :
136622167
Full Text :
https://doi.org/10.1007/s00424-018-02250-3