Exp Mol Med.  2012 Oct;44(10):622-632.

Hepatic STAMP2 decreases hepatitis B virus X protein-associated metabolic deregulation

• Kim HY
• Cho HK
• Yoo SK
• Cheong J

Abstract

Six transmembrane protein of prostate 2 (STAMP2) plays a key role in linking inflammatory and diet-derived signals to systemic metabolism. STAMP2 is induced by nutrients/feeding as well as by cytokines such as TNFalpha, IL-1beta, and IL-6. Here, we demonstrated that STAMP2 protein physically interacts with and decreases the stability of hepatitis B virus X protein (HBx), thereby counteracting HBx-induced hepatic lipid accumulation and insulin resistance. STAMP2 suppressed the HBx-mediated transcription of lipogenic and adipogenic genes. Furthermore, STAMP2 prevented HBx-induced degradation of IRS1 protein, which mediates hepatic insulin signaling, as well as restored insulin-mediated inhibition of gluconeogenic enzyme expression, which are gluconeogenic genes. We also demonstrated reciprocal expression of HBx and STAMP2 in HBx transgenic mice. These results suggest that hepatic STAMP2 antagonizes HBx-mediated hepatocyte dysfunction, thereby protecting hepatocytes from HBV gene expression.

Keyword

fatty liver; gluconeogenesis; hepatitis B virus X protein; insulin resistance; liver; STEAP4 protein, human

MeSH Terms

Animals
Female
Gene Expression
Gluconeogenesis/genetics
Hep G2 Cells
Humans
Insulin/pharmacology/physiology
Insulin Receptor Substrate Proteins/genetics/metabolism
Insulin Resistance
*Lipid Metabolism
Liver/*metabolism/physiopathology
Male
Membrane Proteins/metabolism/*physiology
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Oxidoreductases/metabolism/*physiology
Phosphorylation
Protein Binding
Protein Processing, Post-Translational
Proteolysis
Receptor, Insulin/metabolism
Trans-Activators/*physiology
Transcriptional Activation