TRANSGENIC MICE OVEREXPRESSING THE BETA-1-ADRENERGIC RECEPTOR IN ADIPOSE-TISSUE ARE RESISTANT TO OBESITY

The ratio of alpha- to beta-receptors is thought to regulate the lipol ytic index of adipose depots. To determine whether increasing the acti vity of the beta(1)-adrenergic receptor (AR) in adipose tissue would a ffect the lipolytic rate or the development of this tissue, we used th e enhancer-promoter region of the adipocyte lipid-binding protein (aP2 ) gene to direct expression of the human beta(1)AR cDNA to adipose tis sue. Expression of the transgene was seen only in brown and white adip ose tissue. Adipocytes from transgenic mice were more responsive to be ta AR agonists than were adipocytes from nontransgenic mice, both in t erms of cAMP production and lipolytic rates. Transgenic animals were p artially resistant to diet-induced obesity. They had smaller adipose t issue depots than their nontransgenic littermates, reflecting decrease d lipid accumulation in their adipocytes. In addition to increasing th e lipolytic rate, overexpression of the beta(1)AR induced the abundant appearance of brown fat cells in subcutaneous white adipose tissue. T hese results demonstrate that the beta(1)AR is involved in both stimul ation of lipolysis and the proliferation of brown fat cells in the con text of the whole organism. Moreover, it appears that it is the overal l beta AR activity, rather than the particular subtype, that controls these phenomena.