CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

Figure 6

Proposed mechanism of hepatic steatosis in ACE2 mice. ACE2 deletion causes an imbalance between Ang-(1–7) and AngII with higher levels of the latter. Since Ang-(1–7) via Mas stimulates and AngII via the AT1 receptor inhibits sirtuin 1 expression, this regulatory factor is downregulated. This leads to upregulation of the fatty acid translocase, CD36, and an increased uptake of nonesterified fatty acids (NEFA) into hepatocytes causing ectopic fat deposition and oxidative stress in the liver. Oxidative stress is augmented by direct effects of the decreased sirtuin 1 and the increased AT1-signalling on the formation of reactive oxygen species. In the blood, NEFAs are decreased leading to shrinking adipocytes and fat pads, as well as a drop in body weight.