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Transgenic Mice Overexpressing the ß1-Adrenergic Receptor in Adipose Tissue Are Resistant to Obesity

Department of Microbiology/Cancer Center (V.S., S.R.R.) University of Pennsylvania Philadelphia, Pennsylvania 19104
Department of Biochemistry (V.S.) Department of Physiology and Biophysics (M.M.R.) University of Illinois School of Medicine Chicago, Illinois 60612
Department of Medicine (R.A.G.) University of Chicago Medical School Chicago, Illinois 60637
Dana Farber Cancer Institute and Department of Cell Biology (B.M.S.) Harvard Medical School Boston, Massachusetts 02115

The ratio of - to ß-receptors is thought to regulate the lipolytic index of adipose depots. To determine whether increasing the activity of the ß₁-adrenergic receptor (AR) in adipose tissue would affect the lipolytic rate or the development of this tissue, we used the enhancer-promoter region of the adipocyte lipid-binding protein (aP2) gene to direct expression of the human ß₁AR cDNA to adipose tissue. Expression of the transgene was seen only in brown and white adipose tissue. Adipocytes from transgenic mice were more responsive to ßAR agonists than were adipocytes from nontransgenic mice, both in terms of cAMP production and lipolytic rates. Transgenic animals were partially resistant to diet-induced obesity. They had smaller adipose tissue depots than their nontransgenic littermates, reflecting decreased lipid accumulation in their adipocytes. In addition to increasing the lipolytic rate, overexpression of the ß₁AR induced the abundant appearance of brown fat cells in subcutaneous white adipose tissue. These results demonstrate that the ß₁AR is involved in both stimulation of lipolysis and the proliferation of brown fat cells in the context of the whole organism. Moreover, it appears that it is the overall ßAR activity, rather than the particular subtype, that controls these phenomena.

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