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Life Long High Fat Diet Causes Hepatic Lipid Accumulation by Programming Lipid Synthesis Genes in Liver of Male Rat
Author(s) -
Jung Paul Mark,
Zhou Dan,
Moody Laura,
Kriska Adam,
Chen Hong,
Pan YuanXiang
Publication year - 2016
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.30.1_supplement.850.11
Subject(s) - offspring , medicine , endocrinology , weaning , fatty acid synthase , biology , epigenetics , beta oxidation , fatty liver , lipid metabolism , dna methylation , gene expression , biochemistry , gene , pregnancy , metabolism , genetics , disease
Life long high fat (HF) diet has been shown to cause more hepatic lipid accumulation in offspring as compared to a post‐weaning HF diet. However, it is still unclear what the epigenetic mechanisms are. We hypothesize that a life long HF diet will cause greater hepatic lipid accumulation as compared to a post‐weaning HF diet. The objective of this study is to understand the epigenetic mechanisms of hepatic lipid accumulation as an outcome of life long HF diet. Timed‐pregnant Sprague‐Dawley rats were given either a control (C, 16% fat) or HF (HF, 45% fat) diet during gestation and lactation. Pups from both C and HF mothers were weaned onto the same HF diet, creating two offspring groups: C/HF and HF/HF. Rats were sacrificed at 12 weeks of age and the left lobe of the liver was used for further analysis. Liver histology showed greater hepatic fat accumulation in the HF/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Only glycerol‐3‐phosphate acyltransferase (GPAM) and fatty acid synthase (FASN) showed higher levels of mRNA. DNA methylation of specific genes was analyzed based on data obtained from methyl‐DNA immunoprecipitation with high‐throughput sequencing. Differential methylation was observed for both GPAM and FASN. Our data suggests that life long HF diet increases lipid storage by increased hepatic GPAM and FASN gene expression in male rats, potentially through epigenetic regulation.