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 lipolytic index of adipose depots. To determine whether increasing the activity of the beta 1-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 beta 1 AR 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 beta AR 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 beta 1 AR induced the abundant appearance of brown fat cells in subcutaneous white adipose tissue. These results demonstrate that the beta 1 AR 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 beta AR activity, rather than the particular subtype, that controls these phenomena.
Soloveva
V
V
Department of Microbiology/Cancer Center, University of Pennsylvania, Philadelphia 19104, USA.
Graves
R A
RA
Rasenick
M M
MM
Spiegelman
B M
BM
Ross
S R
SR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000473:pathology; D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D004041:Dietary Fats / Q000633:toxicity; D004280:Dobutamine / Q000494:pharmacology; D002149:Energy Intake; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D019076:Transgenes
D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004041:Dietary Fats; D018342:Receptors, Adrenergic, beta-1; D011993:Recombinant Fusion Proteins; D004280:Dobutamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol