BETA-ADRENERGIC RECEPTORS AND G-PROTEINS IN THE OB OB MOUSE/

The ob/ob mouse white epididymal adipose tissue is endowed with very l ow lipolytic activity, due to abnormally low adenylyl cyclase activati on in response to B-adrenergic agents, The abundance of the two princi pal G-proteins that are responsible for the transduction of adenylyl c yclase is also decreased in several tissues of the ob/ob mouse, compar ed to levels in the lean mouse, By contrast, B-adrenergic receptor lev els appear normal in adipose tissue (Am J Physiol 1992; 263: C121-C129 ) and are elevated in liver (Am J Physiol 1994; 265: C1664-C1672), sug gesting that the diminished abundance of G-proteins was responsible fo r the low lipolytic activity, We reassessed the relative importance of B-adrenergic receptors and G-proteins in view of the discovery of the beta(3)-adrenergic receptor. The major beta-AR isoform in mouse white adipose tissue is the beta(3)-AR and its level is severely decreased in the obese mouse. This indicates that the lipolytic defect in the ob /ob mouse is due to lack of beta(3)-receptor function. Furthermore the extremely high sensitivity of this receptor to the ambient concentrat ions of GTP, explains the lack of response of adenylyl cyclase activit y to the inhibitory effect of GTP in adipose tissue of the ob/ob mouse .