Berlan M, Lafontan M, Dang Tran L
J Physiol (Paris). 1980;76(2):133-46.
Lipolytic activity of human isolated fat cells from different fat deposits was studied. The purpose of the present investigations was to determine the epinephrine responsiveness, with regard to alpha- and beta-adrenergic receptor site activity, of omental and subcutaneous adipocytes (abdominal or from the lateral part of the thigh). Adipocytes were obtained from normal subjects or from obese subjects on iso- or hypocaloric diets. The lipolytic effect of epinephrine varied according to the fat deposits, while the beta-lipolytic effect of isoproterenol was more stable (Fig. 1). We explored the possible involvement of adrenergic alpha-receptors, in order to explain these results. The potentiating action of phentolamine on epinephrine-induced lipolysis, and the antilipolytic effect of alpha-agonists on basal or theophylline--induced lipolysis, were found to be a good indication of alpha-adrenergic activity. The alpha-adrenergic antilipolytic effect was most prominent in adipose tissue from the lateral part of the thigh, and less noticeable in omental adipocytes. In conclusion, the inability of epinephrine to induce lipolysis, and the epinephrine-induced inhibition of lipolysis observed when the basal rate of FFA release was spontaneously increased in subcutaneous fat-cells of the thigh, could be explained by an increased alpha adrenergic responsiveness (Fig. 2). Moreover, various alpha-adrenergic agonists (phenylephrine, noradrenaline and adrenaline) showed a clear inhibiting effect on theophylline-stimulated adipocytes from the thigh. The pharmacological study of the antilipolytic effect of epinephrine on theophylline-induced lipolysis showed that the inhibition was linked to a specific stimulation of the alpha-receptors of the subcutaneous adipocytes (Fig. 4). From the different sets of experiments, it is shown that the modifications in the lipolytic effect of epinephrine on adipocytes of different areas could be explained by the occurrence of a variable alpha-adrenergic effect initiated by catecholamine. Furthermore, theophylline stimulation of lipolysis provides an accurate system to investigate the alpha-inhibiting effect of catecholamines. Our study was completed by the investigation of the lipolytic activity of subcutaneous fat cells from obese subjects submitted to a hypocaloric diet (800-1 000 Cal/day). An increased alpha-inhibitory effect of epinephrine was shown on the increased basal lipolytic activity observed in the fat cells of obese subjects on a hypocaloric diet (Fig. 5); a similar effect was observed when these adipocytes were stimulated by theophylline. To conclude, these investigations allow the alpha-adrenergic effect to be considered as a regulator mechanism of the in vitro lipolytic activity in human adipose tissue, since the antilipolytic effect is operative whenever the basal rate of lipolysis is increased (spontaneously, after caloric restriction, or with a lipolytic agent such as theophylline).
研究了来自不同脂肪沉积部位的人体分离脂肪细胞的脂解活性。本研究的目的是确定网膜和皮下脂肪细胞(腹部或大腿外侧)对肾上腺素的反应性,涉及α和β肾上腺素能受体位点活性。脂肪细胞取自正常受试者或处于等热量或低热量饮食的肥胖受试者。肾上腺素的脂解作用因脂肪沉积部位而异,而异丙肾上腺素的β脂解作用更稳定(图1)。我们探讨了肾上腺素能α受体可能的参与情况,以解释这些结果。酚妥拉明对肾上腺素诱导的脂解的增强作用,以及α激动剂对基础或茶碱诱导的脂解的抗脂解作用,被发现是α肾上腺素能活性的良好指标。α肾上腺素能抗脂解作用在大腿外侧的脂肪组织中最为显著,在网膜脂肪细胞中则不太明显。总之,在大腿皮下脂肪细胞中,当游离脂肪酸释放的基础速率自发增加时,肾上腺素无法诱导脂解以及观察到的肾上腺素诱导的脂解抑制作用,可以通过α肾上腺素能反应性增加来解释(图2)。此外,各种α肾上腺素能激动剂(去氧肾上腺素、去甲肾上腺素和肾上腺素)对来自大腿的茶碱刺激的脂肪细胞显示出明显的抑制作用。肾上腺素对茶碱诱导的脂解的抗脂解作用的药理学研究表明,这种抑制作用与皮下脂肪细胞α受体的特异性刺激有关(图4)。从不同组的实验可以看出,肾上腺素对不同区域脂肪细胞脂解作用的改变可以通过儿茶酚胺引发的可变α肾上腺素能效应来解释。此外,茶碱刺激脂解提供了一个准确的系统来研究儿茶酚胺的α抑制作用。我们的研究通过对接受低热量饮食(800 - 1000卡路里/天)的肥胖受试者的皮下脂肪细胞的脂解活性进行研究而完成。在接受低热量饮食的肥胖受试者的脂肪细胞中观察到基础脂解活性增加时,肾上腺素的α抑制作用增强(图5);当这些脂肪细胞受到茶碱刺激时也观察到类似的效果。总之,这些研究使α肾上腺素能效应被视为人体脂肪组织体外脂解活性的一种调节机制,因为无论脂解基础速率何时增加(自发地、热量限制后或使用脂解剂如茶碱时),抗脂解作用都起作用。