CATECHOLAMINE-INDUCED LIPOLYSIS IN ADIPOSE-TISSUE OF THE ELDERLY
CATECHOLAMINE-INDUCED LIPOLYSIS IN ADIPOSE-TISSUE OF THE ELDERLY
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DOI：
10.1172/jci114612
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发表时间：
1990-05-01
影响因子：
15.9
通讯作者：
ARNER, P
中科院分区：
文献类型：
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作者：
LONNQVIST, F;NYBERG, B;ARNER, P
在25名年轻（21-35岁）和10名老年（58-72岁）健康非肥胖受试者中，使用从腹部皮下组织获得的分离脂肪细胞，研究了儿茶酚胺对脂解作用的依赖性改变。基础脂解不受年龄的影响，而老年受试者中儿茶酚胺刺激的脂解率降低了50%（P < 0.005）。为了阐明这一现象背后的机制，用在脂解级联中明确定义的步骤起作用的试剂刺激脂解，从受体到最后一步：蛋白激酶/脂肪酶敏感性脂肪酶复合物的活化。所有药物在老年人中刺激脂解的速率比年轻受试者低50%（P < 0.05或更低）。然而，两组中脂解剂的半数最大有效浓度相似。α 2-肾上腺素受体激动剂的抗脂解作用在年轻和老年受试者中也是相同的。此外，β-和α 2-受体的化学计量特性不随年龄的增加而改变。对相同个体进行的体内研究同样表明，尽管血浆去甲肾上腺素正常升高，但老年受试者在运动期间的脂解反应性受损，血浆甘油浓度降低50%（P < 0.05）。青年和老年人血浆甘油水平与儿茶酚胺刺激的体外脂解所引起的甘油释放均呈显著正相关（r = 0.8-0.9，P < 0.001）。总之，减少激活的脂肪酶敏感的复合物似乎是一个迟钝的脂肪分解反应的机制，在老年受试者的儿茶酚胺刺激。这一发现可以解释年龄依赖性的脂肪分解反应降低运动在体内。
Age-dependent alterations in the effects of catecholamines on lipolysis were investigated in 25 young (21-35 yr) and 10 elderly (58-72 yr) healthy, nonobese subjects using isolated adipocytes obtained from abdominal subcutaneous tissue. Basal lipolysis was not affected by aging, while the rate of catecholamine-stimulated lipopolysis was reduced by 50% in the elderly subjects (P < 0.005). To elucidate the mechanisms behind this phenomenon lipolysis was stimulated with agents that act at well-defined steps in the lipolytic cascade, from the receptor down to the final step: the activation of the protein kinase/hormone-sensitive lipase complex. All agents stimulated lipolysis at a 50% lower rate in elderly as compared with young subjects (P < 0.05 or less). However, half-maximum effective concentrations of the lipolytic agents were similar in both groups. The antilipolytic effects of alpha2-adrenoceptor agonists were also the same in young and old subjects. Moreover, the stoichiometric properties of the beta- and alpha2-receptors did not change with increasingage. In vivo studies performed on the same individuals likewise demonstrated an impaired lipolytic responsiveness, with 50% lower plasma glycerol concentrations during exercise in the elderly subjects (P < 0.05), in spite of a normal rise in plasma norepinephrine. The plasma glycerol levels correlated strongly to the glycerol release caused by catecholamine-stimulated lipolysis in vitro in both young and elderly subjects (r = 0.8-0.9, P < 0.001). In conclusion, a decreased activation of the hormone-sensitive lipase complex appears to be the mechanism underlying a blunted lipolytic response of fat cells to catecholamine stimulation in elderly subjects. This finding may, explain the age-dependent decreased lipolytic response to exercise in vivo.