High fat diet causes hepatic lipid accumulation by programming lipid synthesizing genes via gene body methylation
type: CreativeWork
description: A high-fat diet (HFD) has been shown to cause more hepatic lipid accumulation as compared to a low-fat control (C) diet. However, it is still unclear what role epigenetic mechanisms play in hepatic lipid accumulation. We hypothesize that a HFD will cause greater hepatic lipid accumulation through increased lipid synthesizing gene expression via decreased gene methylation. The objective of this study is to determine the role of methylation in hepatic lipid synthesizing genes as an outcome of hepatic lipid accumulation due to a HFD. Two models were used to address the following: the direct effects of a post-weaning HFD on hepatic lipid synthesizing genes as well as the indirect effects of a maternal HFD. Timed-pregnant Sprague-Dawley rats were given either a C (16% fat) or HFD (45% fat) during gestation and lactation. Pups from both C mothers were weaned onto either a C or HFD and the pups from the maternal HFD were weaned onto a HFD, creating three offspring groups: C/C, C/HF, and HF/HF. Model 1 compared the C/C group to the C/HF group, while model 2 focused on the comparison of the C/HF group to the HF/HF group. Rats were sacrificed at 12 weeks of age, and the left lobe of the liver was used for further analysis. In model 1, liver histology showed greater hepatic fat accumulation in the C/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Glycerol-3-phosphate acyltransferase (GPAM), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and glucose-6-phosphotase (G6Pase) showed lower levels of mRNA in the C/HF group as compared to the C/C group. DNA methylation of those genes was analyzed based on data obtained from methyl-DNA immunoprecipitation with high-throughput sequencing (MEDIP-SEQ). Differential methylation was observed for G6Pase, GPAM, and ACC1. GPAM and ACC1 showed decreased average methylation read peaks for C/HF in comparison to…
abstract: A high-fat diet (HFD) has been shown to cause more hepatic lipid accumulation as compared to a low-fat control (C) diet. However, it is still unclear what role epigenetic mechanisms play in hepatic lipid accumulation. We hypothesize that a HFD will cause greater hepatic lipid accumulation through increased lipid synthesizing gene expression via decreased gene methylation. The objective of this study is to determine the role of methylation in hepatic lipid synthesizing genes as an outcome of hepatic lipid accumulation due to a HFD. Two models were used to address the following: the direct effects of a post-weaning HFD on hepatic lipid synthesizing genes as well as the indirect effects of a maternal HFD. Timed-pregnant Sprague-Dawley rats were given either a C (16% fat) or HFD (45% fat) during gestation and lactation. Pups from both C mothers were weaned onto either a C or HFD and the pups from the maternal HFD were weaned onto a HFD, creating three offspring groups: C/C, C/HF, and HF/HF. Model 1 compared the C/C group to the C/HF group, while model 2 focused on the comparison of the C/HF group to the HF/HF group. Rats were sacrificed at 12 weeks of age, and the left lobe of the liver was used for further analysis. In model 1, liver histology showed greater hepatic fat accumulation in the C/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Glycerol-3-phosphate acyltransferase (GPAM), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and glucose-6-phosphotase (G6Pase) showed lower levels of mRNA in the C/HF group as compared to the C/C group. DNA methylation of those genes was analyzed based on data obtained from methyl-DNA immunoprecipitation with high-throughput sequencing (MEDIP-SEQ). Differential methylation was observed for G6Pase, GPAM, and ACC1. GPAM and ACC1 showed decreased average methylation read peaks for C/HF in comparison to…
author: Jung, Paul M
language: en
keywords: Epigenetics, Nutrient-gene interaction, Nonalcoholic fatty liver disease, Obesity
date published: 2018-03-02T19:59:46Z
date modified: 2026-07-22T22:24:37Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/99124