Stelmanska Ewa, Szrok Sylwia, Swierczynski Julian
Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland.
Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland.
J Steroid Biochem Mol Biol. 2015 Mar;147:31-9. doi: 10.1016/j.jsbmb.2014.11.017. Epub 2014 Nov 20.
Decreased lipolytic activity in adipose tissue may be one of the reasons behind excess accumulation of body fat during pregnancy. The aim of this study was to analyze the effect of progesterone on the expression of: (a) Lipe (encoding hormone-sensitive lipase, HSL), (b) Pnpla2 (encoding adipose triglyceride lipase, ATGL), (c) abhydrolase domain containing 5 (Abhd5), and (d) G0/G1 switch 2 (G0s2) genes in white adipose tissue (WAT), as potential targets for progesterone action during the course of pregnancy. Administration of progesterone to female rats, which was reflected by approximately 2.5-fold increase in circulating progesterone concentration, is associated with a decrease in Lipe gene expression in the inguinal WAT. The expression of Pnpla2 gene in all main fat depots of females and males remained unchanged after progesterone administration. Administration of progesterone resulted in an increase in the expression of Abhd5 gene (whose product increases ATGL activity) and G0s2 gene (whose product decreases ATGL activity) in the inguinal WAT of female rats. Mifepristone, a selective antagonist of progesterone receptor, abolished the effect of progesterone on Lipe, Abhd5 and G0s2 genes expression in the inguinal WAT. The decrease in Lipe and the increase in Abhd5 and G0s2 genes expression was associated with lower rate of stimulated lipolysis. Administration of progesterone exerted no effect on Lipe, Abhd5 and G0s2 genes expression and stimulated lipolysis in the retroperitoneal WAT of females, as well as in the inguinal, epididymal and retroperitoneal WAT of males. In conclusion, our findings suggest that progesterone decreases the rate of lipolysis in the inguinal WAT of female rats, inhibiting the activity of both ATGL (by stimulating synthesis of G0S2 - specific inhibitor of the enzyme) and HSL (due to inhibition of Lipe gene expression).
脂肪组织中脂解活性降低可能是孕期体脂过度积累的原因之一。本研究的目的是分析孕酮对白色脂肪组织（WAT）中以下基因表达的影响：（a）Lipe（编码激素敏感性脂肪酶，HSL）、（b）Pnpla2（编码脂肪甘油三酯脂肪酶，ATGL）、（c）含水解酶结构域5（Abhd5）和（d）G0/G1开关2（G0s2）基因，这些基因是孕期孕酮作用的潜在靶点。给雌性大鼠注射孕酮后，循环孕酮浓度增加了约2.5倍，这与腹股沟WAT中Lipe基因表达的降低有关。给雌性和雄性大鼠注射孕酮后，所有主要脂肪库中Pnpla2基因的表达均未发生变化。给雌性大鼠注射孕酮后，腹股沟WAT中Abhd5基因（其产物可增加ATGL活性）和G0s2基因（其产物可降低ATGL活性）的表达增加。孕酮受体的选择性拮抗剂米非司酮消除了孕酮对腹股沟WAT中Lipe、Abhd5和G0s2基因表达的影响。Lipe表达的降低以及Abhd5和G0s2基因表达的增加与刺激脂解的速率降低有关母鼠腹膜后WAT以及公鼠腹股沟、附睾和腹膜后WAT中，孕酮对Lipe、Abhd5和G0s2基因表达以及刺激脂解均无影响。总之，我们的研究结果表明，孕酮降低了雌性大鼠腹股沟WAT中的脂解速率，抑制了ATGL（通过刺激G0S2的合成——该酶的特异性抑制剂）和HSL（由于Lipe基因表达受到抑制）的活性。
