Nunes Patricia Pereira, Andreotti Sandra, de Fátima Silva Flaviane, Sertié Rogério Antonio Laurato, Caminhotto Rennan de Oliveira, Komino Ayumi Cristina Medeiros, Reis Gabriela Boltes, Lima Fabio Bessa
Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Life Sci. 2017 Dec 1;190:29-35. doi: 10.1016/j.lfs.2017.09.030. Epub 2017 Sep 25.
Most studies developed to investigate the effects of glucocorticoids chronic treatment on white adipose tissue uses high doses of these hormones. This study analyzes some effects of a chronic, continuous and steady infusion of low-dose hydrocortisone and the relationship with lipid accumulation in white adipose depots in rats.
Nineteen male Wistar rats were divided into control (CON) and cortisol (CORT) groups. Along six weeks CORT group received continuous infusion of 0.6mg/kg/day of hydrocortisone, while CON group received saline. After euthanasia, subcutaneous and visceral (retroperitoneal and mesenteric) fat pads were excised, weighted and analyzed for: lipogenic enzymes activity; molecular changes of 11-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme; enzymes involved in lipid uptake, incorporation, and metabolism and in fatty acids esterification. Besides, morphometric cell analysis was performed.
CORT group showed increased triglycerides, changes in lipoprotein profile and 26,8% increment in central subcutaneous (SC) mass, while visceral fat pads masses remained unchanged. Adipocytes from SC, only, presented increased fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase activity, in addition to reduced AMP-activated protein kinase and 11βHSD1 enzymes content.
Chronic low-dose hydrocortisone treatment consequences seem to be different from those commonly seen in long term hypercortisolism. While high doses promote lipid accumulation in visceral depots, a low dose showed an increase in central SC depot only. This appears to involve an increment in lipid storage and in de novo lipogenesis enzymes activity.
大多数旨在研究糖皮质激素长期治疗对白色脂肪组织影响的研究使用的是高剂量这些激素。本研究分析了低剂量氢化可的松慢性、持续且稳定输注的一些作用及其与大鼠白色脂肪库中脂质积累的关系。
将19只雄性Wistar大鼠分为对照组(CON)和皮质醇组(CORT)。在六周时间里,CORT组接受0.6mg/kg/天氢化可的松的持续输注,而CON组接受生理盐水。安乐死后,切除皮下和内脏(腹膜后和肠系膜)脂肪垫,称重并分析:生脂酶活性;11β - 羟基类固醇脱氢酶1型(11βHSD1)酶的分子变化;参与脂质摄取、掺入、代谢以及脂肪酸酯化的酶。此外,进行了细胞形态计量分析。
CORT组甘油三酯增加,脂蛋白谱发生变化,中央皮下(SC)脂肪量增加26.8%,而内脏脂肪垫重量不变。仅SC的脂肪细胞脂肪酸合酶、ATP - 柠檬酸裂解酶和葡萄糖 - 6 - 磷酸脱氢酶活性增加,同时AMP激活的蛋白激酶和11βHSD1酶含量降低。
慢性低剂量氢化可的松治疗的后果似乎与长期皮质醇增多症中常见的不同。高剂量促进内脏脂肪库中的脂质积累,而低剂量仅使中央SC脂肪库增加。这似乎涉及脂质储存增加和从头脂肪生成酶活性增加。