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- Title
The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis Abnormality Induced by Hepatitis C Virus Infection.
- Authors
Jizheng Chen; Ning Wang; Mei Dong; Min Guo; Yang Zhao; Zhiyong Zhuo; Chao Zhang; Xiumei Chi; Yu Pan; Jing Jiang; Hong Tang; Junqi Niu; Dongliang Yang; Zhong Li; Xiao Han; Qian Wang; Xinwen Chen; Chen, Jizheng; Wang, Ning; Dong, Mei
- 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.
- Subjects
METABOLIC regulation; HISTONE deacetylase; GLUCOSE; HOMEOSTASIS; HEPATITIS C; FORKHEAD transcription factors; GLUCONEOGENESIS; GLUCOSE metabolism; ENZYME inhibitors; PROTEIN metabolism; RNA metabolism; ENZYME metabolism; ANIMAL experimentation; ANIMALS; CELL lines; ENZYMES; GENES; HYDROLASES; INSULIN resistance; LIVER; MEMBRANE proteins; METABOLISM; MICE; NEEDLE biopsy; PHOSPHORYLATION; PROTEINS; RNA; CHRONIC hepatitis C; CHEMICAL inhibitors
- Publication
Diabetes, 2015, Vol 64, Issue 12, p4088
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-0197