Abstract
Background and Aim. Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.
Highlights
In conjunction with the growing epidemics of obesity and type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) becomes a common cause of chronic liver diseases in China [1]
Forty rats were randomly divided into four groups: (1) a normal control (NC) group (n = 10) was fed with the standard chow and gavaged with normal saline; (2) a HFD group (n = 10) was fed with the HFD (15 g lard oil and 2 g pure cholesterol were fixed to 83 g standard chow, SLAC Laboratory Animal Co., Ltd., Shanghai, China) and gavaged with normal saline; (3) a pioglitazone control (PC) group (n = 10) was fed with the standard chow and gavaged with pioglitazone (10 mg/kg per day; Conba Pharmaceutical Co., Ltd., Zhejiang, China) [15]; and (4) a high-fat diet plus pioglitazone treatment (HP) group (n = 10) was fed with the HFD and gavaged with pioglitazone (10 mg/kg per day)
Significant improvement was observed in steatosis, lobular inflammation, and hepatocyte ballooning in the HP group compared with the HFD group
Summary
In conjunction with the growing epidemics of obesity and type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) becomes a common cause of chronic liver diseases in China [1]. TZDs, such as rosiglitazone and pioglitazone, have been demonstrated to improve insulin resistance (IR) and hepatic steatosis in NASH [4]. Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues
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