Ovariectomy in mice decreases lipid metabolism-related gene expression in adipose tissue and skeletal muscle with increased body fat

Abstract

Postmenopausal women as well as rodents after ovariectomy, which results in a lack of estrogen, can become obese. Ovariectomy-induced obesity in mice is associated with a decrease in oxygen consumption, indicating repressed energy expenditure. In this study, to elucidate the mechanism of weight gain after ovariectomy, we examined the expression patterns of genes related to energy expenditure and lipid metabolism, in mouse tissues including adipose tissue and skeletal muscle. In adipose tissue and skeletal muscle, at 2-4 wk after ovariectomy, levels of nuclear receptors and cofactors involved in energy expenditure such as ERR1, PPARα and PPARδ, and PGC1α and PGC1β were lower than in control mice. mRNA levels of their targets, medium-chain acyl coenzyme A dehydrogenase and acetyl CoA oxidase, enzymes for fatty acid β-oxidation, were lower. In addition, the expression of PPARγ and SREBP1, transcription factors important for lipogenesis, was decreased, as well as that of acetyl CoA carboxylase and fatty acid synthase, enzymes for fatty acid synthesis, and diacyl glycerol acetyl transferase 1 and 2, enzymes for triglyceride synthesis. These changes in gene expression are consistent with the obese phenotype in mice after ovariectomy. Thus a decrease in the expression of energy expenditure-related genes in adipose tissue and skeletal muscle could, in part, be responsible for obesity after ovariectomy.