CD36Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

Abstract EN

Background and Aims.

Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system.

Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE 2 - / y ) mice.

Methods.

Male C57BL/6 and ACE 2 - / y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis.

Results.

ACE 2 - / y mice showed lower body weight and white adipose tissue at all ages investigated.

Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma.

Strikingly, ACE 2 - / y mice showed high deposition of lipids in the liver.

Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE 2 - / y mice.

Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1.

ACE 2 - / y mice also showed impairments in glucose metabolism and insulin signaling in the liver.

Conclusions.

Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis.