Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats
Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats
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DOI：
10.1111/apha.12226
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发表时间：
2014-06-01
影响因子：
6.3
通讯作者：
Lima, F. B.
中科院分区：
文献类型：
--
作者：
Chimin, P.;Farias, T. da S. M.;Lima, F. B.
过量的糖皮质激素（GC）促进脂肪组织从周围到中心部位的再分配。在本研究中，我们描述了长时间GC过量的实验条件，并研究了其对白色脂肪组织脂质代谢的影响。方法将20只雄性Wistar大鼠分为对照组（CON）和地塞米松治疗组（DEX）。DEX组给予地塞米松(0.25mgkg（-1)day(-1)）治疗4周，CON组给予生理盐水治疗。动物被杀死，皮下（SC）、腹膜后（RP）和肠系膜（MS）脂肪垫被切除、称重并进行脂肪细胞分离、形态测定细胞分析和将葡萄糖掺入脂质中。结果DEX组血浆皮质酮水平下降58%，肾上腺萎缩19%，有效阻断下丘脑-垂体-肾上腺轴。DEX组出现胰岛素抵抗、葡萄糖耐受不良、血脂异常，胰岛素、瘦素水平升高，脂肪细胞肥大。他们发现RP和MS仓库的脂肪生成增加，葡萄糖与三酰甘油脂肪酸的结合增加。脂源酶atp -柠檬酸裂解酶、脂肪酸合成酶、葡萄糖-6-磷酸脱氢酶和苹果酸活性仅在DEX组的MS脂肪库中有所增加，而这些酶的基因表达在SC和MS脂肪库中均有所增加。结论GC处理促进脂肪代谢的适应性主要是由于提供脂肪生成所需NADPH的酶的活性增加，而不是直接处理脂肪酸合成本身的酶的活性增加。
AimGlucocorticoid (GC) in excess promotes the redistribution of adipose tissue from peripheral to central sites of the body. In this study, we characterized an experimental condition of prolonged GC excess and investigated its effect on the lipogenic metabolism in white adipose tissue.MethodsTwenty male Wistar rats were divided into control (CON) and dexamethasone-treated (DEX) groups. DEX group received dexamethasone (0.25mgkg(-1)day(-1)) during 4weeks, while CON group received saline. Animals were killed and subcutaneous (SC), retroperitoneal (RP) and mesenteric (MS) fat pads were excised, weighed and processed for adipocyte isolation, morphometric cell analysis and incorporation of glucose into lipids.ResultsThe treatment effectively blocked hypothalamic-pituitary-adrenal axis, as verified by a 58% decrease in plasma corticosterone levels and 19% atrophy in adrenal glands in DEX group. Animals from DEX group presented insulin resistance, glucose intolerance, dyslipidaemia and increased insulin and leptin plasma levels and hypertrophied adipocytes. They showed increased lipogenesis in RP and MS depots, with increased incorporation of glucose into fatty acids of triacylglycerol. Increased activity of lipogenic enzymes ATP-citrate lyase, fatty acid synthase, glucose-6-phosphate dehydrogenase and malic was only seen in the MS depot in DEX group, while gene expression of these enzymes was enhanced in SC and MS fat depots.ConclusionThe adaptations promoted by GC treatment in adipose metabolism seemed to be mainly due to the increased activity of enzymes that supply the NADPH required for lipogenesis than to the increase in enzymes that more directly deal with fatty acid synthesis itself.