Beta-adrenergic-cyclic AMP signalling pathway modulates cell function at the transcriptional level in 3T3-F442A...

We studied the role of cAMP in the regulation of the expression of the adipsin gene and of some other adipose-specific genes including lipoprotein lipase (LPL), glycerophosphate dehydrogenase (G3PDH), and adipocyte P2 (aP2) in 3T3-F442A adipocytes. Northern blot analysis of isoproterenol (10(-6) M)-, forskolin (10(-5) M)- or 8-bromo-cAMP (10(-3) M)-treated adipocytes showed that the steady-state levels of adipsin mRNA were strongly reduced in a time-dependent and reversible manner. The concentration of isoproterenol giving a half-maximal effect in the down-regulation of the adipsin message was approximately 5 x 10(-8) M. Similarly, cell treatment by forskolin elicited a down-regulation of LPL and G3PDH mRNA levels but did not alter aP2 mRNA level. As determined by nuclear run-on assays, the rate of transcription of adipsin, LPL and G3PDH in isoproterenol-treated adipocytes was respectively 3, 3, and 2 times lower than in control adipocytes. These results indicate (1) that cAMP plays a dominant antilipogenic role in the fat cell through the transcriptional down-regulation of the expression of two major genes involved in triglyceride biosynthesis; (2) that cAMP does not reverse the adipocyte character; (3) hence, that cAMP suppresses adipsin expression at the transcriptional level, providing additional support for the role of adipsin protein in adipocyte metabolism.