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诱导型米色脂肪细胞改善肩胛间 BAT 切除小鼠受损的葡萄糖代谢。

Inducible beige adipocytes improve impaired glucose metabolism in interscapular BAT-removal mice.

机构信息

Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Department of Experimental Center for Basic Medical Teaching, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

出版信息

Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Mar;1866(3):158871. doi: 10.1016/j.bbalip.2020.158871. Epub 2020 Dec 18.

Abstract

Inducible beige adipocytes are emerging as an interesting issue in obesity and metabolism research. There is a neglected possibility that brown adipocytes are equally activated when external stimuli induce the formation of beige adipocytes. Thus, the question is whether beige adipocytes have the same functions as brown adipocytes when brown adipose tissue (BAT) is lacking. This question has not been well studied. Therefore we determine the beneficial effects of beige adipocytes upon cold challenge or CL316243 treatments in animal models of interscapular BAT (iBAT) ablation by surgical denervation. We found that denervated iBAT were activated by cold exposure and CL316243 treatments. The data show that beige adipocytes partly contribute to the improvement of impaired glucose metabolism resulting from denervated iBAT. Thus, we further used iBAT-removal animal models to abolish iBAT functions completely. We found that beige adipocytes upon cold exposure or CL316243 treatments improved impaired glucose metabolism and enhanced glucose uptake in iBAT-removal mice. The insulin signaling was activated in iBAT-removal mice upon cold exposure. Both the activation of insulin signaling and up-regulation of glucose transporter expression were observed in iBAT-removal mice with CL316243 treatments. The data show that inducible beige adipocytes may have different mechanisms to improve impaired glucose metabolism. Inducible beige adipocytes can also enhance energy expenditure and lipolytic activity of white adipose tissues when iBAT is lacking. We provide direct evidences for the beneficial effect of inducible beige adipocytes in glucose metabolism and energy expenditure in the absence of iBAT in vivo.

摘要

诱导型米色脂肪细胞在肥胖和代谢研究中是一个备受关注的问题。有一种被忽视的可能性,即当外部刺激诱导米色脂肪细胞形成时,棕色脂肪细胞也会被同等激活。因此,问题是当棕色脂肪组织(BAT)缺失时,米色脂肪细胞是否具有与棕色脂肪细胞相同的功能。这个问题还没有得到很好的研究。因此,我们通过外科去神经支配来确定在肩胛间 BAT(iBAT)消融的动物模型中,冷刺激或 CL316243 处理对诱导型米色脂肪细胞的有益作用。我们发现去神经支配的 iBAT 可以被冷暴露和 CL316243 处理激活。数据表明,米色脂肪细胞部分有助于改善由于 iBAT 去神经支配而导致的葡萄糖代谢受损。因此,我们进一步使用 iBAT 切除动物模型来完全消除 iBAT 的功能。我们发现,冷暴露或 CL316243 处理诱导的米色脂肪细胞改善了 iBAT 切除小鼠的葡萄糖代谢受损,并增强了 iBAT 切除小鼠的葡萄糖摄取。冷暴露可激活 iBAT 切除小鼠的胰岛素信号。在 iBAT 切除小鼠中,用 CL316243 处理后,观察到胰岛素信号的激活和葡萄糖转运体表达的上调。这些数据表明,诱导型米色脂肪细胞可能具有改善葡萄糖代谢受损的不同机制。在 iBAT 缺失的情况下,诱导型米色脂肪细胞还可以增强白色脂肪组织的能量消耗和脂解活性。我们提供了在体内缺乏 iBAT 的情况下,诱导型米色脂肪细胞在葡萄糖代谢和能量消耗方面有益作用的直接证据。

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