The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis Abnormality Induced by Hepatitis C Virus Infection.

Abstract:

:Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HDAC3. Specifically, HDAC9 expression can be strongly induced upon hepatitis C virus (HCV) infection. HCV-induced HDAC9 upregulation enhances gluconeogenesis by promoting the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, indicating a major role for HDAC9 in the development of HCV-associated exaggerated gluconeogenic responses. Moreover, HDAC9 expression levels and gluconeogenic activities were elevated in livers from HCV-infected patients and persistent HCV-infected mice, emphasizing the clinical relevance of these results. Our results suggest HDAC9 is involved in glucose metabolism, HCV-induced abnormal glucose homeostasis, and type 2 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Chen J,Wang N,Dong M,Guo M,Zhao Y,Zhuo Z,Zhang C,Chi X,Pan Y,Jiang J,Tang H,Niu J,Yang D,Li Z,Han X,Wang Q,Chen X

doi

10.2337/db15-0197

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

4088-98

issue

12

eissn

0012-1797

issn

1939-327X

pii

db15-0197

journal_volume

64

pub_type

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