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Institut National de la Santé et de la Recherche Médicale U 478, Faculté de Médecine Xavier Bichat, 75870 Paris, France
By use of
targeted oncogenesis, a brown adipocyte cell line was derived from a
hibernoma of a transgenic mouse carrying the proximal promoter of the
human mineralocorticoid receptor (MR) linked to the SV40 large T
antigen. T37i cells remain capable of differentiating into brown
adipocytes upon insulin and triiodothyronine treatment as judged by
their ability to express uncoupling protein 1 and maintain MR
expression. Aldosterone treatment of undifferentiated cells induced
accumulation of intracytoplasmic lipid droplets and mitochondria. This
effect was accompanied by a significant and dose-dependent increase in
intracellular triglyceride content (half-maximally effective dose
10
9 M) and involved MR, because it was unaffected by
RU-38486 treatment but was totally abolished in the presence of
aldosterone antagonists (spironolactone, RU-26752). The expression of
early adipogenic gene markers, such as lipoprotein lipase, peroxisome
proliferator-activated receptor-
, and adipocyte-specific fatty acid
binding protein 2, was enhanced by aldosterone, confirming activation
of the differentiation process. We demonstrate that, in the T37i cell
line, aldosterone participates in the very early induction of brown
adipocyte differentiation. Our findings may have a broader biological
significance and suggest that MR is not only implicated in maintaining
electrolyte homeostasis but could also play a role in metabolism and
energy balance.
uncoupling proteins; peroxisome proliferator-activated receptor-
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