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High Fat Diet Induces Expression of Cell Cycle Control Gene p16 In the Liver of Obesity Prone Rats Through Epigenetic Modifications
Author(s) -
Zhang Xiyuan,
Pan YuanXiang
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.212.4
Subject(s) - epigenetics , biology , endocrinology , chromatin , chromatin immunoprecipitation , medicine , obesity , cell cycle , western blot , gene expression , population , histone , cell growth , gene , cell , promoter , genetics , environmental health
Objectives Proliferation of cells is important in the repair and growth of tissues. Our bodies' ability to regenerate tissues decreases as we age. Because of ongoing epidemics of obesity and type 2 diabetes, it's important to find out if high fat diet affects liver regenerate function in obese population. Methods Obesity Prone (OP) and Obesity Resistant (OR) rats were fed with high fat diet containing 45 kcal% fat, 35 kcal% carbohydrate and 20 kcal% protein for 3 months. To investigate whether cell cycle control genes were affected by high fat diet, livers from both OP and OR rats were collected and used to isolate RNA, protein, and chromatin. Quantitative real‐time PCR, Western blot and chromatin immunoprecipitation were performed for the analysis of the cell cycle genes. Results Our analysis demonstrates for the first time that high fat diet causes a five‐fold increase of p16 (Ink4a) mRNA (p=0.03) in the liver of male OP rats. Acetylation of histone H4, but not H3, at the promoter region is also significantly increased in male OP rats (p=0.003), which may reveal the molecular mechanism of p16 up‐regulation. Conclusions Expression of p16 (Ink4a) increases with age in tissues. Significant increase of p16 expression level in the liver of OP rats by high fat diet suggests that high fat diet may lead to an decline in the regenerative capabilities of the liver maintained by p16 (Ink4a). Grant Funding Source: USDA