Reduced Histone H3K9 Acetylation of Clock Genes and Abnormal Glucose Metabolism in ob ob Mice

Recent chronobiological studies found significant correlation between lack of clock function and metabolic abnormalities. We previously showed that clock gene expressions were dampened in the peripheral tissues of obese and diabetic ob ob mice. However, the molecular mechanism of the disturbance rem...

Full description

Saved in:
Bibliographic Details
Published in:Chronobiology international 2012-10, Vol.29 (8), p.982-993
Main Authors: Ishikawa-Kobayashi, Eiko, Ushijima, Kentarou, Ando, Hitoshi, Maekawa, Tomohiro, Takuma, Masashi, Furukawa, Yusuke, Fujimura, Akio
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Acetylation
Adipose tissue
Adipose Tissue - metabolism
Animals
Chromatin
Clock genes
CLOCK Proteins - genetics
CLOCK Proteins - metabolism
Dbp
Deoxyglucose
Diabetes
Epigenetics
Gene Expression Regulation - physiology
Glucose - metabolism
Histone acetylation
Histone deacetylase inhibitor
Histone Deacetylase Inhibitors
Histones - genetics
Histones - metabolism
Liver - metabolism
Mice
Mice, Inbred C57BL
Mice, Obese
Promoter Regions, Genetic
Real-Time Polymerase Chain Reaction
RNA - genetics
RNA - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Recent chronobiological studies found significant correlation between lack of clock function and metabolic abnormalities. We previously showed that clock gene expressions were dampened in the peripheral tissues of obese and diabetic ob ob mice. However, the molecular mechanism of the disturbance remained to be determined. In this study, we demonstrated for the first time that acetylation levels of histone H3 lysine 9 (H3K9) at the promoter regions of clock genes, such as Dbp, Per2, and Bmal1, in the adipose tissue of ob ob mice were significantly reduced compared with those of its control C57BL 6J mice. Treatment with histone deacetylase (HDAC) inhibitors increased Dbp, but not Per2 or Bmal1, mRNA expression in adipose tissue, and it decreased blood glucose in these animals. In addition, 2-deoxyglucose uptake activity was significantly suppressed by silencing Dbp expression in cultured adipocytes. These results suggest that reduced H3K9 acetylation and subsequent decreased mRNA expression of the Dbp gene in adipose tissue are involved in the mechanism of development of abnormal glucose metabolism in ob ob mice. (Author correspondence: akiofuji@jichi.ac.jp)
ISSN:0742-0528
1525-6073
DOI:10.3109/07420528.2012.706765