Endogenous catalase delays high-fat diet-induced liver injury in mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and PGC1α mRNA expression were decreased in both CKO and WT mice at HFD feeding, GSK3β phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

Effect of cassava flour on the lipidic and redox profile of Wistar rats with dyslipidemia

“…In physiological situations, there is a basal amount of catalase, which creates a redox balance between oxidants and antioxidants in the body (Barroso et al, 2019). Our CAT results agree with literature, once it has been already established that there is an inverse relationship between catalase activity and damage caused by high‐fat and high‐cholesterol diet consumption (Piao, Choi, Kwon, & Ha, 2017).…”

Inactivation of SREBP-1a Phosphorylation Prevents Fatty Liver Disease in Mice: Identification of Related Signaling Pathways by Gene Expression Profiles in Liver and Proteomes of Peroxisomes

“…Furthermore, PPARA, HNF4a, or peroxisomal ACOX-1 expression differences were of the highest enrichments indicating the well-characterized integrative expression network of gene expression of peroxisomal target genes [ 40 , 41 ]. In line with a previous report of a protective effect of endogenous catalase activity in fatty liver [ 42 ], a further novel finding of our study was the observation that half of the genes that center around SREBP-1 and differ in regulation according to the ability of SREBP-1a to be phosphorylated are correlated with peroxisomal catalase activity. These included genes like CWF19L1, which was previously shown to act in fatty liver and metabolic diseases [ 43 , 44 , 45 , 46 ].…”

Glycine Increases Insulin Sensitivity and Glutathione Biosynthesis and Protects against Oxidative Stress in a Model of Sucrose‐Induced Insulin Resistance

“…The dysregulation of insulin sensitivity in SF rats may occur at high concentration of H 2 O 2 , because hydrogen peroxide, in the presence of hyperinsulinemia, was reported to have a significant negative effect on insulin signaling and to cause a selective phosphorylation in serine/threonine and loss of IRS1 and 2 proteins which further inhibit insulin response in mammalian skeletal muscle [ 33 , 34 ]. Moreover, mitochondrial catalase in transgenic mice and endogenous catalase protect against high levels of H 2 O 2 generation and delay high-fat diet-induced liver injury by improving glucose tolerance and insulin sensitivity in mice [ 35 , 36 ]. Nevertheless, H 2 O 2 at physiological concentration is exclusively regulated by GPXs and has been described to mediate signaling regulation of glucose metabolism [ 37 ].…”