Trayhurn P, Duncan J S, Rayner D V, Hardie L J
Division of Biochemical Sciences, Rowett Research Institute, Bucksburn, Aberdeen, Scotland, United Kingdom.
Biochem Biophys Res Commun. 1996 Nov 12;228(2):605-10. doi: 10.1006/bbrc.1996.1704.
The acute effect of two selective beta 3-adrenoceptor agonists, BRL 35135A and ZD2079, on the expression of the ob gene and plasma leptin levels has been examined in mice. By 4-5 h after the administration of either beta 3-agonist to lean animals there was a major loss of ob mRNA from epididymal white adipose tissue. This was accompanied by a substantial fall in circulating leptin levels, as measured by an ELISA. Even 24 h after the first administration of beta 3-agonists, ob mRNA levels and circulating leptin levels remained low. In contrast to lean animals, treatment with BRL 35135A had only a minor effect on ob mRNA levels in obese (ob/ob) mice. Regulation of leptin production appears to involve a negative feedback loop to white adipose tissue through the sympathetic nervous system suppressing ob gene transcription via beta 3-adrenoceptors; an impairment in this loop is evident in the ob/ob mutant.
在小鼠中研究了两种选择性β3-肾上腺素能受体激动剂BRL 35135A和ZD2079对ob基因表达及血浆瘦素水平的急性影响。给瘦小鼠注射任一β3-激动剂后4 - 5小时，附睾白色脂肪组织中的ob mRNA大量减少。通过酶联免疫吸附测定法（ELISA）检测发现，与此同时循环瘦素水平大幅下降。即使在首次注射β3-激动剂24小时后，ob mRNA水平和循环瘦素水平仍维持在低水平。与瘦小鼠不同，用BRL 35135A处理对肥胖（ob/ob）小鼠的ob mRNA水平仅有轻微影响。瘦素产生的调节似乎涉及通过交感神经系统对白色脂肪组织的负反馈回路，该回路通过β3-肾上腺素能受体抑制ob基因转录；在ob/ob突变体中，这一回路存在明显缺陷。
