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

Abstract

BACKGROUND & AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: 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
• Journal: Journal of hepatology (J Hepatol) Vol. 63 Issue 2 Pg. 477-85 (Aug 2015) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25646886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Membrane Proteins
• Tiarp protein, mouse
• RNA

Topics

• Animals
• Biopsy
• Blotting, Western
• Cells, Cultured
• Disease Models, Animal
• Gene Expression Regulation
• Humans
• Insulin Resistance (genetics)
• Lipid Metabolism
• Liver (metabolism, pathology)
• Male
• Membrane Proteins (biosynthesis, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Non-alcoholic Fatty Liver Disease (genetics, metabolism)
• RNA (genetics)
• Reverse Transcriptase Polymerase Chain Reaction