1312 Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats With High Fat Diet-Induced Non-Alcoholic Steatohepatitis

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.

Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane?

“…Individuals with diabetes mellitus not only have increased susceptibility to but also higher morbidity and mortality due to coronavirus disease 2019 (COVID-19).The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin converting enzyme (ACE)2 as a co-receptor to enter the cell [ 1 ]. Among anti-diabetic agents, liraglutide and pioglitazone [ 2 ], and among anti-hypertensives, ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB) [ 3 ], have been shown in some animal studies to upregulate the tissue expression of ACE2. This has led to the speculation that use of these medications might increase susceptibility to, and severity of, COVID-19.…”

“…Recent publications have alluded to upregulation of ACE2 by pioglitazone [ 7 ]. Indeed, animal studies have shown that pioglitazone increases the expression of ACE2 in the liver, adipose tissue and skeletal muscles [ 2 ]. However, pioglitazone was found to have no effect on cardiac ACE2 expression in a study on db/db mice [ 8 ].…”