| First Author | Tao XR | Year | 2019 |
| Journal | J Lipid Res | Volume | 60 |
| Issue | 12 | Pages | 1983-1995 |
| PubMed ID | 31604805 | Mgi Jnum | J:296296 |
| Mgi Id | MGI:6466629 | Doi | 10.1194/jlr.M093252 |
| Citation | Tao XR, et al. (2019) Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis. J Lipid Res 60(12):1983-1995 |
| abstractText | Nonalcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that the renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of the RAS, decreased angiotensinogen (AGT) profoundly impacts RAS bioactivity. Here, we investigated the role of hepatocyte-derived AGT in liver steatosis. AGT floxed mice (hepAGT(+/+)) and hepatocyte-specific AGT-deficient mice (hepAGT(-/-)) were fed a Western diet and a normal laboratory diet for 12 weeks, respectively. Compared with hepAGT(+/+) mice, Western diet-fed hepAGT(-/-) mice gained less body weight with improved insulin sensitivity. The attenuated severity of liver steatosis in hepAGT(-/-) mice was evidenced by histologic changes and reduced intrahepatic triglycerides. The abundance of SREBP1 and its downstream molecules, acetyl-CoA carboxylase and FASN, was suppressed in hepAGT(-/-) mice. Furthermore, serum derived from hepAGT(+/+) mice stimulated hepatocyte SREBP1 expression, which could be diminished by protein kinase B (Akt)/mammalian target of rapamycin (mTOR) inhibition in vitro. Administration of losartan did not affect diet-induced body weight gain, liver steatosis severity, and hepatic p-Akt, p-mTOR, and SREBP1 protein abundance in hepAGT(+/+) mice. These data suggest that attenuation of Western diet-induced liver steatosis in hepAGT(-/-) mice is associated with the alternation of the Akt/mTOR/SREBP-1c pathway. |
