Deletion of retinoic acid-related orphan receptor gamma reduces body weight and hepatic lipids in mice by modulating the expression of lipid metabolism genes

Abstract

Aim: Retinoic acid-related orphan receptor γ (RORγ) functions as a ligand-dependent transcription factor and its loss has been shown to affect the circadian expression of lipid metabolism genes. However, its effect on body weight gain and hepatic lipids is not well understood. In this study, we investigated the impact of Rorγ gene deletion on changes in body weight and hepatic lipids.

Methods: Body weight and lipids were analyzed in the plasma and liver. Expression of lipid metabolism genes in the liver was evaluated in wild type and Rorγ knockout mice.

Results: We show that deletion of RORγ results in reduced body weight and fewer lipids in the liver. Analysis of gene expression showed that deletion of Rorγ resulted in an overall lower expression of genes and transcription factors involved in lipid biosynthesis. We observed a decrease in the gene expression of cholesterol biosynthesis, efflux, and esterification but an increase in bile acid synthesis. There was a decrease in fatty acid and triglycerides biosynthesis genes and an increase in the fatty acid uptake genes. The decrease in the expression of lipid biosynthesis genes was accompanied by the decrease in the sterol response element binding protein (Srebp) genes. We observed an increase in the expression of peroxisome proliferator-activated receptor alpha (Ppara) and a decrease in the expression of acetyl-CoA carboxylase 2 (Acc2) genes.

Conclusion: Our data suggest that RORγ regulates body weight and lipid metabolism genes and its modulation may be beneficial for the management of obesity and related lipid metabolic disorders.

Keywords

Lipid metabolism / triglycerides / retinoic acid-related orphan receptor γ / peroxisome proliferator-activated receptors / sterol response element binding proteins

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