Bégin-Heick N
Department of Biochemistry, University of Ottawa, Canada.
Int J Obes Relat Metab Disord. 1996 Mar;20 Suppl 3:S32-5.
The ob/ob mouse white epididymal adipose tissue is endowed with very low lipolytic activity, due to abnormally low adenylyl cyclase activation in response to beta-adrenergic agents. The abundance of the two principal G-proteins that are responsible for the transduction of adenylyl cyclase is also decreased in several tissues of the ob/ob mouse, compared to levels in the lean mouse. By contrast, beta-adrenergic receptor levels appear normal in adipose tissue (Am J Physiol 1992; 263: C121-C129) and are elevated in liver (Am J Physiol 1994; 265: C1664-C1672), suggesting that the diminished abundance of G-proteins was responsible for the low lipolytic activity. We reassessed the relative importance of beta-adrenergic receptors and G-proteins in view of the discovery of the beta 2-adrenergic receptor. The major beta-AR isoform in mouse white adipose tissue is the beta 3-AR and its levels is severely decreased in the obese mouse. This indicates that the lipolytic defect in the ob/ob mouse is due to lack of beta 3-receptor function. Furthermore the extremely high sensitivity of this receptor to the ambient concentrations of GTP, explains the lack of response of adenylyl cyclase activity to the inhibitory effect of GTP in adipose tissue of the ob/ob mouse.
ob/ob小鼠的白色附睾脂肪组织具有极低的脂解活性，这是由于其对β-肾上腺素能药物的反应中腺苷酸环化酶激活异常低下所致。与瘦小鼠相比，负责腺苷酸环化酶转导的两种主要G蛋白在ob/ob小鼠的多个组织中的丰度也降低。相比之下，β-肾上腺素能受体水平在脂肪组织中似乎正常（《美国生理学杂志》1992年；263：C121 - C129），而在肝脏中升高（《美国生理学杂志》1994年；265：C1664 - C1672），这表明G蛋白丰度的降低是脂解活性低下的原因。鉴于β2 - 肾上腺素能受体的发现，我们重新评估了β-肾上腺素能受体和G蛋白的相对重要性。小鼠白色脂肪组织中的主要β-AR亚型是β3-AR，其水平在肥胖小鼠中严重降低。这表明ob/ob小鼠的脂解缺陷是由于缺乏β3-受体功能。此外，该受体对环境中GTP浓度的极高敏感性，解释了ob/ob小鼠脂肪组织中腺苷酸环化酶活性对GTP抑制作用缺乏反应的原因。
