Carbenoxolone alters the morphology of adipose tissues and downregulates genes involved in adipogenesis, glucose transport and lipid metabolism in high-fat diet-fed mice.
Carbenoxolone alters the morphology of adipose tissues and downregulates genes involved in adipogenesis, glucose transport and lipid metabolism in high-fat diet-fed mice.
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Carbenoxolone 改变高脂肪饮食喂养小鼠脂肪组织的形态，并下调参与脂肪形成、葡萄糖转运和脂质代谢的基因。
DOI：
10.1055/s-0031-1297990
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Ohzeki,T
中科院分区：
文献类型：
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作者：
Sano,S;Nakagawa,Y;Yamaguchi,R;Fujisawa,Y;Satake,E;Nagata,E;Nakanishi,T;Liu,Y-J;Ohzeki,T
糖皮质激素（GC）过量会促进脂肪组织堆积，11β-羟基类固醇脱氢酶1型（11β-HSD1）在GC的局部放大中发挥重要作用。因此，在本研究中，我们研究了11β-HSD1抑制剂卡苯索隆（CBX）对高脂（HF）饮食喂养小鼠内脏脂肪形态变化以及参与脂肪形成和脂质代谢的基因表达的影响。小鼠从 5 周龄起开始接受 HF 饮食。 10 周龄时，小鼠每天接受 CBX 或载体腹腔注射，持续 2 周。 CBX 降低了 HF 喂养小鼠的体重和内脏脂肪量，并提高了胰岛素敏感性。这伴随着脂肪细胞尺寸的减小和内脏脂肪中大尺寸脂肪细胞的减少。 CBX 小鼠中脂肪生成（PPARγ 和 C/EBPα）、葡萄糖转运（GLUT4）和脂质代谢（LPL、ATGL 和 HSL）相关基因的表达受到抑制。 CBX 治疗诱导内脏脂肪有益的形态变化，并降低脂肪生成、葡萄糖转运和脂质代谢相关基因的表达。这些发现揭示了 CBX 减少脂肪堆积和提高胰岛素敏感性的潜在机制。
Glucocorticoid (GC) excess promotes adipose tissue accumulation, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in the local amplification of GC. Therefore, in this study, we investigated the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, on morphological changes in visceral fat, and the expression of genes involved in adipogenesis and lipid metabolism in high-fat (HF) diet-fed mice. Mice were fed a HF diet from 5 weeks of age. At 10 weeks of age, the mice received an intraperitoneal injection of CBX or vehicle every day for 2 weeks. CBX decreased body weight and visceral fat mass, and improved insulin sensitivity in HF-fed mice. This was accompanied by reduced adipocyte size and a decrease in large-sized adipocytes in visceral fat. The expression of adipogenesis (PPARγandC/EBPα), glucose transport (GLUT4) and lipid metabolism (LPL,ATGL, andHSL)-related genes were suppressed in CBX mice. CBX treatment induced beneficial morphological changes in visceral fat and decreased the expression of adipogenesis, glucose transport and lipid metabolism-related genes. These findings reveal a potential mechanism underling the effects of CBX on reduced fat accumulation and improved insulin sensitivity.