Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), an amplifier of local glucocorticoid activity, has been shown to modulate white adipose tissue (WAT) metabolism and function. In this study, we investigated the roles of 11β-HSD1 in regulating BAT function. We observed a significant increase in the expression of BAT-specific genes, including UCP1, Cidea, Cox7a1, and Cox8b, in BVT.2733 (a selective inhibitor of 11β-HSD1)-treated and 11β-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11β-HSD1 was overexpressed, which effect was reversed by BVT.2733 treatment. Consistent with the in vitro results, expression of a range of genes related to brown fat function in high-fat diet-fed mice treated with BVT.2733. Our results indicate that 11β-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity.

译文

:棕色脂肪组织(BAT)增加能量消耗,并且是肥胖症的诱人治疗靶标。 11β-羟基类固醇脱氢酶1(11β-HSD1)是一种局部糖皮质激素活性的放大器,已被证明可调节白色脂肪组织(WAT)的代谢和功能。在这项研究中,我们调查了11β-HSD1在调节BAT功能中的作用。我们观察到在BVT.2733(11β-HSD1的选择性抑制剂)治疗和小鼠缺乏11β-HSD1的原代棕色脂肪细胞中,BAT特异性基因(包括UCP1,Cidea,Cox7a1和Cox8b)的表达显着增加。相比之下,当11β-HSD1过表达时,褐色脂肪细胞中BAT特异性基因表达显着下降,这种作用被BVT.2733处理所逆转。与体外结果一致,在用BVT.2733处理的高脂饮食喂养小鼠中,一系列与棕色脂肪功能有关的基因的表达。我们的结果表明,11β-HSD1可以作为重要的调节剂,控制与棕色脂肪功能相关的基因的表达,因此可能成为预防肥胖的潜在靶标。

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