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Src family kinases suppress differentiation of brown adipocytes and browning of white adipocytes

机译:Src家族激酶抑制棕色脂肪细胞分化和白色脂肪细胞褐变

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摘要

Brown adipocytes and beige adipocytes can expend energy, generate heat, and increase whole-body energy expenditure. The detailed mechanisms of adipogenesis and thermogenesis of these cells are still obscure. Here, we show that Src family kinases (SFKs) regulate both brown adipogenesis and browning of white adipocytes. To identify factors involved in brown adipogenesis, we first examined the effect of several chemical inhibitors on the differentiation of brown preadipocytes isolated from mouse brown adipose tissue (BAT) and found that treatment with PP2, the specific inhibitor of SFKs, promoted the differentiation. Another inhibitor of SFKs, PP1, also promoted the brown adipogenesis, whereas an inactive analogue of PP2, PP3, did not. Moreover, over-expression of C-terminal Src kinase (CSK), the negative regulator of SFKs, also promoted brown adipogenesis. Next, we examined the effect of inhibition of SFKs on the differentiation of white preadipocytes isolated from white adipose tissue (WAT). Our results showed that either PP2 treatment or CSK-over-expression generated Ucp1-positive beige adipocytes, thus inducing browning of white adipocytes. Finally, our analysis showed that the expression levels and activity of SFKs in WAT were much higher than in BAT. These results taken together suggest that SFKs regulate differentiation and browning of fat cells in vivo.
机译:棕色脂肪细胞和米色脂肪细胞会消耗能量,产生热量并增加全身能量消耗。这些细胞的脂肪形成和生热的详细机制仍不清楚。在这里,我们显示Src家族激酶(SFKs)调节棕色脂肪形成和白色脂肪细胞褐变。为了确定参与棕色脂肪形成的因素,我们首先检查了几种化学抑制剂对从小鼠棕色脂肪组织(BAT)分离的棕色前脂肪细胞分化的影响,并发现用SFKs的特异性抑制剂PP2的治疗促进了分化。 SFK的另一种抑制剂PP1也促进褐色脂肪形成,而PP2的无活性类似物PP3则没有。此外,C末端Src激酶(CSK)(SFKs的负调节剂)的过表达也促进了褐色脂肪形成。接下来,我们研究了SFK抑制对从白色脂肪组织(WAT)分离的白色前脂肪细胞分化的影响。我们的结果表明,PP2处理或CSK过表达都会产生Ucp1阳性的米色脂肪细胞,从而诱导白色脂肪细胞褐变。最后,我们的分析表明,WAT中SFK的表达水平和活性远高于BAT。这些结果加在一起表明,SFKs在体内调节脂肪细胞的分化和褐变。

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