RGD Reference Report - Hypermethylation of hepatic glucokinase and L-type pyruvate kinase promoters in high-fat diet-induced obese rats. - Rat Genome Database

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Hypermethylation of hepatic glucokinase and L-type pyruvate kinase promoters in high-fat diet-induced obese rats.

Authors: Jiang, M  Zhang, Y  Liu, M  Lan, MS  Fei, J  Fan, W  Gao, X  Lu, D 
Citation: Jiang M, etal., Endocrinology. 2011 Apr;152(4):1284-9. doi: 10.1210/en.2010-1162. Epub 2011 Jan 14.
RGD ID: 7488967
Pubmed: PMID:21239437   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2010-1162   (Journal Full-text)

Obesity-dependent insulin resistance and type 2 diabetes mellitus are closely associated with decreased glucose utilization and down-regulation of hepatic glycolytic enzymes expression. Previously, we showed that DNA hypermethylation is involved in age-dependent susceptibility to hepatic insulin resistance and diabetes. However, what we cannot distinguish is whether the age-related obesity contributes to DNA hypermethylation in those natural aging rats. In the present study, we hypothesize that DNA methylation plays a crucial role in the regulation of glycolytic enzymes in the high-fat diet-induced obesity. Here, we report that DNA hypermethylation is correlated with a decline in hepatic glucokinase (Gck) and L-type pyruvate kinase (LPK) expression in high-fat diet-induced obese rats as compared with the control diet group. Down-regulation of Gck and LPK expression are reversed by the 5-aza-2'-deoxycytidine in the cell model of steatosis. These novel observations indicate that DNA methylation is involved in the development of metabolic diseases, such as obesity, insulin resistance, type 2 diabetes mellitus, and nonalcoholic steatohepatitis, suggesting that the hypermethylation level of Gck and LPK promoters may be a useful parameter for the evaluation of obesity-induced insulin resistance and fatty liver.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity  ISOGck (Rattus norvegicus)7488967; 7488967DNA more ...RGD 
obesity  IDA 7488967DNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gck  (glucokinase)

Genes (Mus musculus)
Gck  (glucokinase)

Genes (Homo sapiens)
GCK  (glucokinase)


Additional Information