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Effects of ß-Adrenoceptor Subtype Stimulation on obese Gene Messenger Ribonucleic Acid and on Leptin Secretion in Mouse Brown Adipocytes Differentiated in Culture¹

Departments of Medical Biochemistry and Physiology (J.S.), University Medical Center, Geneva, Switzerland

Address all correspondence and requests for reprints to: Dr. J.-P. Giacobino, Département de Biochimie Médicale, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland. E-mail: Giacobin{at}CMU.Unige.ch

The ob gene product is known to control food intake and energy expenditure. To determine whether thermogenic agents directly control ob gene expression, the effects of ß-adrenoceptor agonists on the level of the ob gene messenger RNA (mRNA) and on leptin secretion have been studied in mouse brown adipocytes differentiated in culture. These cells highly expressed the ß₃-adrenoceptor, the uncoupling protein, and the ob gene mRNAs. The ob gene was expressed in mouse brown adipocytes earlier than in mouse white adipocytes under the same culture conditions and to a similar level. The ß₃-, ß₁-, and ß₂-adrenoceptor agonists BRL 37344, dobutamine, and terbutaline inhibited ob gene expression in mouse brown adipocytes differentiated in culture with EC₅₀ values of 0.3, 1.0, and 85 nM, respectively. Leptin secretion by the cells under basal conditions was 78 ± 10 pg/µg DNA·4 h and was decreased by exposure to the ß-adrenoceptor agonists. The ob gene mRNA half-life was 9.4 h and was decreased to 2.4 h by 1 nM BRL 37344, indicating that the inhibitory effect of the ß₃-agonist might be due to destabilization of ob gene mRNA. (Bu)₂cAMP (10–100 µM) and forskolin (20 µM) mimicked the effect of the ß-adrenoceptor agonists. FFA (150–800 µM) had only a small inhibitory effect on ob gene mRNA expression. The results suggest the existence in brown adipose tissue of a retroregulatory pathway by which leptin production is inhibited when the sympathetic nervous system is stimulated.

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