Shen G X, Cai W, Angel A
Department of Internal Medicine, The University of Manitoba, Winnipeg, Canada. gshen@.ms.umanitoba.ca
Atherosclerosis. 1998 Sep;140(1):113-20. doi: 10.1016/s0021-9150(98)00128-2.
High levels of cholesteryl ester transfer protein (CETP) favours decreased plasma high density lipoprotein cholesterol and increased levels of cholesterol in apolipoprotein B containing lipoproteins. Adipose tissue is one of the major sources of circulating CETP. Previous studies by our group and others demonstrated that the production of CETP from hamster adipose tissue increases after fasting, a metabolic state known to affect the sympathoadrenal axis. The present study examines the influence of beta-adrenergic agonists on the secretion of CETP from hamster adipose tissue. Fifteen minutes after an intraperitoneal injection of isoproterenol (12 microg/kg), the release of CETP mass and activity from adipose tissue fragments incubated in vitro were significantly increased. This was associated with an elevation in CETP mass and activity in plasma. The effects of isoproterenol on CETP release from adipose tissue and plasma CETP levels were suppressed by propranolol, a beta-adrenoceptor inhibitor. Addition of 10(-6) M isoproterenol to adipose tissue in vitro increased the release of CETP mass and activity from adipose tissue and this was also blocked by propranolol. Isoproterenol-induced secretion of CETP activity from adipose tissue was partially inhibited by cytochalasin B, an inhibitor of actin cytoskeleton reorganization. Forskolin, a classical adenylate cyclase agonist and 8-bromo-cAMP, a functional analogue of cAMP, mimicked the effect of isoproterenol on CETP release from adipose tissue. Our results suggest that isoproterenol increases the secretion of CETP from hamster adipose tissue through a beta-adrenoceptor and a cAMP-dependent pathway. Actin cytoskeleton reorganization may be required for secretion of CETP. The findings imply that the secretion of CETP from adipose tissue is under neurosympathetic control.
高水平的胆固醇酯转运蛋白（CETP）有利于降低血浆高密度脂蛋白胆固醇，并增加载脂蛋白B所含脂蛋白中的胆固醇水平。脂肪组织是循环中CETP的主要来源之一。我们小组和其他研究团队之前的研究表明，禁食后仓鼠脂肪组织中CETP的产生会增加，禁食是一种已知会影响交感肾上腺轴的代谢状态。本研究探讨了β-肾上腺素能激动剂对仓鼠脂肪组织中CETP分泌的影响。腹腔注射异丙肾上腺素（12微克/千克）15分钟后，体外培养的脂肪组织碎片中CETP的质量和活性释放显著增加。这与血浆中CETP的质量和活性升高有关。异丙肾上腺素对脂肪组织中CETP释放和血浆CETP水平的影响被β-肾上腺素能受体抑制剂普萘洛尔所抑制。在体外向脂肪组织中添加10⁻⁶ M异丙肾上腺素会增加脂肪组织中CETP的质量和活性释放，这也被普萘洛尔所阻断。细胞松弛素B（一种肌动蛋白细胞骨架重组抑制剂）部分抑制了异丙肾上腺素诱导的脂肪组织中CETP活性分泌。福斯可林（一种经典的腺苷酸环化酶激动剂）和8-溴-cAMP（cAMP的功能类似物）模拟了异丙肾上腺素对脂肪组织中CETP释放的作用。我们的结果表明，异丙肾上腺素通过β-肾上腺素能受体和cAMP依赖性途径增加仓鼠脂肪组织中CETP的分泌。CETP的分泌可能需要肌动蛋白细胞骨架重组。这些发现意味着脂肪组织中CETP的分泌受神经交感神经控制。
