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Angiotensinogen in Hepatocytes Contributes to Western Diet-induced Liver Steatosis.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of 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 on western diet and 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 down-stream molecules ACC, FASN was suppressed in hepAGT-/- mice. Furthermore, serum derived from hepAGT+/+ mice stimulated hepatocyte SREBP1 expression, which could be diminished by Akt/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 Akt/mTOR/SREBP-1c pathway.

Authors+Show Affiliations

Zhejiang University School of Medicine, China.Zhejiang University School of Medicine, China.University of Kentucky, United States.University of Kentucky, United States.Zhejiang University School of Medicine, China.Zhejiang University School of Medicine, China.Zhejiang University School of Medicine, China.Zhejiang University School of Medicine, China.Zhejiang University School of Medicine, China; wangjianan111@zju.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31604805

Citation

Tao, Xin-Ran, et al. "Angiotensinogen in Hepatocytes Contributes to Western Diet-induced Liver Steatosis." Journal of Lipid Research, 2019.
Tao XR, Rong JB, Lu HS, et al. Angiotensinogen in Hepatocytes Contributes to Western Diet-induced Liver Steatosis. J Lipid Res. 2019.
Tao, X. R., Rong, J. B., Lu, H. S., Daugherty, A., Shi, P., Ke, C. L., ... Wang, J. A. (2019). Angiotensinogen in Hepatocytes Contributes to Western Diet-induced Liver Steatosis. Journal of Lipid Research, doi:10.1194/jlr.M093252.
Tao XR, et al. Angiotensinogen in Hepatocytes Contributes to Western Diet-induced Liver Steatosis. J Lipid Res. 2019 Oct 11; PubMed PMID: 31604805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensinogen in Hepatocytes Contributes to Western Diet-induced Liver Steatosis. AU - Tao,Xin-Ran, AU - Rong,Jia-Bing, AU - Lu,Hong S, AU - Daugherty,Alan, AU - Shi,Peng, AU - Ke,Chang-Le, AU - Zhang,Zhao-Cai, AU - Xu,Yin-Chuan, AU - Wang,Jian-An, Y1 - 2019/10/11/ PY - 2019/02/13/received PY - 2019/10/09/revised PY - 2019/10/11/accepted PY - 2019/10/13/entrez KW - Angiotensinogen KW - Diet and dietary lipids KW - Fatty acid/Biosynthesis KW - Lipid droplets KW - Lipolysis and fatty acid metabolism KW - Non-alcolholic fatty liver disease KW - Nuclear receptors/SREBP KW - Triglycerides JF - Journal of lipid research JO - J. Lipid Res. N2 - Non-alcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of 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 on western diet and 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 down-stream molecules ACC, FASN was suppressed in hepAGT-/- mice. Furthermore, serum derived from hepAGT+/+ mice stimulated hepatocyte SREBP1 expression, which could be diminished by Akt/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 Akt/mTOR/SREBP-1c pathway. SN - 1539-7262 UR - https://www.unboundmedicine.com/medline/citation/31604805/Angiotensinogen_in_Hepatocytes_Contributes_to_Western_Diet-induced_Liver_Steatosis L2 - http://www.jlr.org/cgi/pmidlookup?view=long&pmid=31604805 DB - PRIME DP - Unbound Medicine ER -