Soloveva V, Graves R A, Rasenick M M, Spiegelman B M, Ross S R
Department of Microbiology/Cancer Center, University of Pennsylvania, Philadelphia 19104, USA.
Mol Endocrinol. 1997 Jan;11(1):27-38. doi: 10.1210/mend.11.1.9870.
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.
α受体与β受体的比例被认为可调节脂肪库的脂解指数。为了确定增加脂肪组织中β1 - 肾上腺素能受体（AR）的活性是否会影响脂解速率或该组织的发育，我们利用脂肪细胞脂质结合蛋白（aP2）基因的增强子 - 启动子区域将人β1 AR cDNA定向表达至脂肪组织。转基因的表达仅在棕色和白色脂肪组织中可见。无论是在cAMP产生还是脂解速率方面，转基因小鼠的脂肪细胞对β AR激动剂的反应都比非转基因小鼠的脂肪细胞更敏感。转基因动物对饮食诱导的肥胖有部分抗性。它们的脂肪组织库比其非转基因同窝仔小，这反映出其脂肪细胞中的脂质积累减少。除了提高脂解速率外，β1 AR的过表达还诱导皮下白色脂肪组织中大量棕色脂肪细胞的出现。这些结果表明，在整个生物体的背景下，β1 AR参与了脂解的刺激和棕色脂肪细胞的增殖。此外，似乎是整体的β AR活性而非特定亚型控制着这些现象。
