The mineralocorticoid receptor mediates aldosterone-induced differentiation of T37i cells into brown adipocytes

By use of targeted oncogenesis, a brown adipocyte cell line was derived fro m a hibernoma of a transgenic mouse carrying the proximal promoter of the h uman mineralocorticoid receptor (MR) linked to the SV40 large T antigen. T3 7i cells remain capable of differentiating into brown adipocytes upon insul in and triiodothyronine treatment as judged by their ability to express unc oupling protein 1 and maintain MR expression. Aldosterone treatment of undi fferentiated cells induced accumulation of intracytoplasmic lipid droplets and mitochondria. This effect was accompanied by a significant and dose-dep endent increase in intracellular triglyceride content (half-maximally effec tive dose 10(-9) M) and involved MR, because it was unaffected by RU-38486 treatment but was totally abolished in the presence of aldosterone antagoni sts (spironolactone, RU-26752). The expression of early adipogenic gene mar kers, such as lipoprotein lipase, peroxisome proliferator-activated recepto r-g, and adipocyte-specific fatty acid binding protein 2, was enhanced by a ldosterone, confirming activation of the differentiation process. We demons trate that, in the T37i cell line, aldosterone participates in the very ear ly induction of brown adipocyte differentiation. Our findings may have a br oader biological significance and suggest that MR is not only implicated in maintaining electrolyte homeostasis but could also play a role in metaboli sm and energy balance.