Adipogenic and lipolytic effects of chronic glucocorticoid exposure
Adipogenic and lipolytic effects of chronic glucocorticoid exposure
复制标题
DOI：
10.1152/ajpcell.00045.2010
复制
发表时间：
2011-01-01
影响因子：
5.5
通讯作者：
Riddell, Michael C.
中科院分区：
文献类型：
--
作者：
Campbell, Jonathan E.;Peckett, Ashley J.;Riddell, Michael C.
坎贝尔JE，Peckett AJ，D‘Souza AM，Hawke TJ，Riddell MC。慢性糖皮质激素暴露的成脂和降脂作用。Am J Physiol Cell Physiol 300：C198-C209,2011。首次发表于2010年10月6日；DOI：10.1152/ajpcell.00045.2010。糖皮质激素被认为在脂肪组织中既具有成脂作用，又具有脂肪分解作用，尽管目前尚不清楚这些作用是否可以同时发生。在这里，我们研究了皮质酮(CORT)在体外和体内对脂肪组织代谢的影响。CORT以浓度依赖的方式促进3T3-L1前脂肪细胞分化，但不增加脂肪细胞的脂肪生成。皮质醇以浓度依赖的方式增加脂肪细胞内的脂解作用(在1-10mM时效果最好)。令人惊讶的是，皮质醇的去除进一步增加了脂解率(类似于对照组的320%，P<；0.05)，这表明对基础脂解有残留作用。皮质醇处理48h后，脂肪甘油三酯脂肪酶基因和蛋白表达增加，激素敏感脂肪酶磷酸化状态(Ser563/Ser660)增加。为了在体内测试这些反应，将含/不含皮质醇(300 Mg)的蜡丸植入SD大鼠皮下。10天后取出脂肪库，进行体外培养。在喂食和禁食条件下，皮质醇治疗组大鼠的游离脂肪酸和甘油浓度均升高。尽管脂肪分解增加，但CORT大鼠的内脏脂肪比假手术大鼠更多(10.2g/kg体重比6.9g/kg体重，P<；0.05)。CORT大鼠内脏脂肪细胞较假手术大鼠小而多，提示脂肪形成是通过前脂肪细胞分化而不是脂肪细胞肥大来实现的。皮下脂肪细胞培养中，皮下脂肪细胞的基础脂解率是假手术大鼠的1.5倍(P<；0.05)。综上所述，我们的研究结果表明，慢性糖皮质激素暴露刺激内脏脂肪组织中的脂肪分解和脂肪生成，但主要通过前脂肪细胞分化促进脂肪生成。
Campbell JE, Peckett AJ, D'souza AM, Hawke TJ, Riddell MC. Adipogenic and lipolytic effects of chronic glucocorticoid exposure. Am J Physiol Cell Physiol 300: C198-C209, 2011. First published October 6, 2010; doi: 10.1152/ajpcell.00045.2010.Glucocorticoids have been proposed to be both adipogenic and lipolytic in action within adipose tissue, although it is unknown whether these actions can occur simultaneously. Here we investigate both the in vitro and in vivo effects of corticosterone (Cort) on adipose tissue metabolism. Cort increased 3T3-L1 preadipocyte differentiation in a concentration-dependent manner, but did not increase lipogenesis in adipocytes. Cort increased lipolysis within adipocytes in a concentration-dependent manner (maximum effect at 1-10 mu M). Surprisingly, removal of Cort further increased lipolytic rates (similar to 320% above control, P < 0.05), indicating a residual effect on basal lipolysis. mRNA and protein expression of adipose triglyceride lipase and phosphorylated status of hormone sensitive lipase (Ser563/Ser660) were increased with 48 h of Cort treatment. To test these responses in vivo, Sprague-Dawley rats were subcutaneously implanted with wax pellets with/without Cort (300 mg). After 10 days, adipose depots were removed and cultured ex vivo. Both free fatty acids and glycerol concentrations were elevated in fed and fasting conditions in Cort-treated rats. Despite increased lipolysis, Cort rats had more visceral adiposity than sham rats (10.2 vs. 6.9 g/kg body wt, P < 0.05). Visceral adipocytes from Cort rats were smaller and more numerous than those in sham rats, suggesting that adipogenesis occurred through preadipocyte differentiation rather than adipocyte hypertrophy. Visceral, but not subcutaneous, adipocyte cultures from Cort-treated rats displayed a 1.5-fold increase in basal lipolytic rates compared with sham rats (P < 0.05). Taken together, our findings demonstrate that chronic glucocorticoid exposure stimulates both lipolysis and adipogenesis in visceral adipose tissue but favors adipogenesis primarily through preadipocyte differentiation.