Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model

Nov 24, 2004Gene

Liver gene activity in mice with long-term high-fat diet obesity

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Twelve weeks of a high-fat diet resulted in significant changes in the expression of 97 hepatic genes in mice.

Body weight, visceral fat accumulation, and circulating cholesterol levels significantly increased in mice on a high-fat diet compared to those on a low-fat diet.
The expression of genes related to fatty acid breakdown and ketone body production increased in the high-fat diet group.
In contrast, genes associated with fat and cholesterol production showed a significant decrease in expression in the high-fat diet group.
Genes involved in stress responses and defense mechanisms were notably more prominent in mice fed a high-fat diet.
Several previously unrecognized regulatory molecules were also altered due to high-fat diet exposure.

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To understand the molecular mechanisms underlying alterations in the pathophysiologic status of dietary obesity, we examined hepatic genes differentially expressed in a long-term high-fat intake-induced obesity mouse model. C57BL/6J male mice were fed with two kinds of diets for 12 weeks; a low-fat diet (LFD), a high-fat diet (HFD; n=8), and the expression levels of approximately 10,000 transcripts in liver tissues from the two groups were assessed using cDNA microarray analysis. Twelve-week feeding with the HFD resulted in significant increase in body weight, visceral fat accumulation and circulating cholesterol concentration, compared with the LFD group. The cDNA microarray analysis revealed marked differences in the expressions of 97 hepatic genes. These genes were categorized into seven groups:metabolism; defense, stress, and inflammation responses; signal transduction, apoptosis, and cell cycle; transcription regulation; protein synthesis and modification; transport; and cellular adhesion, cytoskeleton and trafficking. The expression of genes involved in fatty acid catabolism and ketone body synthesis, such as acyl-CoA oxidase1 (Acox1) and HMG-CoA lyase (Hmgcl), was significantly increased, and expression of genes involved in lipogenesis and cholesterol synthesis, such as acetyl-CoA synthetase2 (Acs2), fatty acid synthase (Fasn), and squalene epoxidase (Sqle), was drastically decreased in the HFD group. Interestingly, the genes implicated in defense and stress responses, such as glutathione S-transferases (GSTs) and heat shock proteins (Hsps), were also highly represented in the HFD group. Besides, a number of previously unappreciated regulatory molecules were changed by the HFD. These results revealed a transcriptional adaptation to long-term HFD and provided interesting information about the molecules involved in the development and maintenance of the obesity phenotype in vivo.

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Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model

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