Prostatic Androgen-Repressed Message-1 as a Regulator of Adipocyte Differentiation in the Mouse

Abstract

Adipocyte differentiation is an important aspect in energy homeostasis. Although the regulation of adipocyte differentiation is relatively well understood, the underlying molecular mechanism remains unclear. In this study, subcutaneous and epididymal adipose tissues were used to study the differential expression of associated genes. We found that the expression level of mouse homologue of rat prostatic androgen-repressed message-1 (mPARM-1) gene was higher in subcutaneous, perirenal and mesenteric adipose tissues than in epididymal adipose tissue. In mouse subcutaneous, perirenal, and mesenteric adipose tissues, the expression level of this gene was higher in adipocytes than in non-adipocyte cells, i.e. stromal-vascular cells. Furthermore, mPARM-1 mRNA expression was up-regulated in subcutaneous, mesenteric, and epididymal adipose tissues of mice fed a high-fat diet compared to those fed a normal-fat diet. Expression level of mPARM-1 mRNA increased in the early stage of the chemically induced adipocyte differentiation, preceding the increase in peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma2) mRNA. Tumor necrosis factor-alpha (TNF-alpha), an inhibitor of adipocyte differentiation, reduced the expression of mPARM-1 mRNA in differentiated 3T3-L1 cells and subsequently down-regulated the expression of adipogenic genes, including PPAR-gamma2, leptin and adipogenin. Moreover, knockdown of mPARM-1 expression with siRNA reduced lipid accumulation and the expression levels of PPAR-gamma2 and adipocyte protein 2 mRNAs, which suggest that the degree of adipocyte differentiation of 3T3-L1 cells has been reduced. These results indicate that mPARM-1 might be involved in the regulation of fat accumulation and adipocyte differentiation.