Beta-adrenergic receptors and G-proteins in the ob/ob mouse.

The ob/ob mouse white epididymal adipose tissue is endowed with very low lipolytic activity, due to abnormally low adenylyl cyclase activation in response to beta-adrenergic agents. The abundance of the two principal G-proteins that are responsible for the transduction of adenylyl cyclase is also decreased in several tissues of the ob/ob mouse, compared to levels in the lean mouse. By contrast, beta-adrenergic receptor levels appear normal in adipose tissue (Am J Physiol 1992; 263: C121-C129) and are elevated in liver (Am J Physiol 1994; 265: C1664-C1672), suggesting that the diminished abundance of G-proteins was responsible for the low lipolytic activity. We reassessed the relative importance of beta-adrenergic receptors and G-proteins in view of the discovery of the beta 2-adrenergic receptor. The major beta-AR isoform in mouse white adipose tissue is the beta 3-AR and its levels 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 concentrations of GTP, explains the lack of response of adenylyl cyclase activity to the inhibitory effect of GTP in adipose tissue of the ob/ob mouse.