Regulation of malic-enzyme-gene expression by cAMP and retinoic acid in differentiating brown adipocytes

Brown adipose tissue (BAT) is composed of highly specialized cells, whose main function is to produce heat under adrenergic stimulation, uncoupling oxidative phosphorylation. For this function, lipogenesis must be accurately regulated. Malic enzyme has a central role in lipogenesis and is strongly expressed in brown adipocytes. In this work, we study the modulation by adrenergic stimuli, cAMP effectors and retinoic acid on the induction produced by insulin and 3,5,3'-triiodothyronine on malic-enzyme-gene expression. Primary cultures of differentiating brown adipocytes have been used. The results obtained demonstrate that physiological doses of norepinephrine do not modify malic-enzyme mRNA levels when acting alone, but considerably reduce the induction produced by insulin, 3,5,3'-triiodothyronine or both together. Other cAMP inducers such as glucagon, forskolin or 8-bromo-cAMP, greatly inhibit both, basal and 3,5,3'-triiodothyronine-induced malic-enzyme-gene gene expression. Retinoic acid abolishes basal and also inhibits 3,5,3'-triiodothyronine-induced malic-enzyme-gene expression.