Of mice and women: the beta 3-adrenergic receptor leptin and obesity

The metabolic response of adipose tissue to stimuli leading to lipid mobilization is important in determining the direction of metabolism and the degree to which adipose tissue can store lipids and release fatty acids in times of need. The lipolytic machinery is controlled by the activity of hormone-sensitive lipase, which in turn is controlled by the cellular levels of cAMP. The production of cAMP is abnormal in the adipose tissue of some animal models of obesity. In the ob/ob mouse, the defective cAMP production has been associated with deficient levels of some of the isoforms of the guanine nucleotide transducing G-proteins and also with the low expression and functionality of the beta 3-adrenergic receptor (beta 3-AR). The recent discovery of the ob gene product leptin calls into question the role of the ob gene in the regulation of the cAMP cascade in adipose tissue. The importance of the beta 3-AR and leptin in regulating human adipose tissue metabolism remains to be clarified.