Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes

Uncoupling proteins (UCP), specific mitochondrial proton transporters that function by uncoupling oxidative metabolism from ATP synthesis, are involve d in thermoregulation and control of energy expenditure. The hibernoma-deri ved T37i cells, which possess functional endogenous mineralocorticoid recep tors (MR), can undergo differentiation into brown adipocytes. In differenti ated T37i cells, UCP1 mRNA levels increased 10- to 20-fold after retinoic a cid or beta -adrenergic treatment. Interestingly, UCP2 and UCP3 mRNA was al so detected. Aldosterone treatment induced a drastic decrease in isoprotere nol- and retinoic acid-stimulated UCP1 mRNA levels in a time- and dose-depe ndent manner (IC50 approximate to 1 nM aldosterone). This inhibition was un affected by cycloheximide and did not modify UCP1 mRNA stability (half-life time = 5 h), indicating that it occurs at the transcriptional level. It in volves both the MR and/or the glucocorticoid receptor (GR), depending on th e retinoic or catecholamine induction pathway. Basal UCP3 expression was al so significantly reduced by aldosterone, whereas UCP2 mRNA levels were not modified. Finally, as demonstrated by JC1 aggregate formation in living cel ls, aldosterone restored mitochondrial membrane potential abolished by isop roterenol or retinoic acid. Our results demonstrate that MR and GR inhibit expression of UCP1 and UCP3, thus participating in the control of energy ex penditure.