Hepatic STAMP2 alleviates high fat diet-induced hepatic steatosis and insulin resistance.

Most studies on the role of STAMP2 in metabolism have used adipose tissue. Little knowledge exists concerning the role of STAMP2 in the liver, which is a metabolically central target. We hypothesized that STAMP2 is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. We examined our hypothesis using human NAFLD patient pathology samples and a high-fat diet (HFD)-induced NAFLD mouse model. The molecular mechanism underlying hepatic STAMP2-mediated lipid imbalance was explored using an oleic acid (OA)-induced NAFLD in vitro model. Noticeably, the expression level of STAMP2 protein was reduced in the livers obtained from NAFLD patients and HFD-induced NAFLD mice. In vivo knockdown of hepatic STAMP2 by siRNA accelerated hepatic steatosis and insulin resistance in mice fed a HFD. Conversely, the delivery of adenoviral STAMP2 (Ad-STAMP2) improved hepatic steatosis in HFD-induced NAFLD mice. The expression of lipogenic or adipogenic factors was increased in both in vitro and in vivo NAFLD models but was reversed by Ad-STAMP2. Adenoviral overexpression of STAMP2 improved insulin resistance in the HFD-induced NAFLD mice. In vivo and in vitro assays demonstrated that STAMP2 modulates insulin sensitivity and glucose metabolism and that STAMP2 counteracts OA-induced insulin resistance by modulating insulin receptor substrate-1 stability. The present study revealed that hepatic STAMP2 plays a pivotal role in preventing HFD-induced NAFLD and that STAMP2 overexpression improves hepatic steatosis and insulin resistance in NAFLD. Our findings indicate that STAMP2 may represent a suitable target for interventions targeting NAFLD. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Citation

Hye Y Kim, So Y Park, Mi H Lee, Jee H Rho, Yoo J Oh, Hye U Jung, Seung H Yoo, Na Y Jeong, Hye J Lee, SungHwan Suh, Su Y Seo, JaeHun Cheong, Jin S Jeong, Young H Yoo. Hepatic STAMP2 alleviates high fat diet-induced hepatic steatosis and insulin resistance. Journal of hepatology. 2015 Aug;63(2):477-85

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PMID: 25646886

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