Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Biochem Biophys Res Commun. 2018 Nov 30;506(3):485-491. doi: 10.1016/j.bbrc.2018.10.034. Epub 2018 Oct 21.
Bcl2l13 is a member of the Bcl-2 family that has been found to play a central role in regulating apoptosis. Recently Bcl2l13 has been reported to induce mitophagy as a functional mammalian homolog of Atg32. However, the role of Bcl2l13 in adipose tissue has not been investigated yet. In the present study, we found that Bcl2l13 expression was increased in white adipose tissue browning process stimulated by cold exposure or β3-adrenergic agonist CL-316,243 in vivo as well as during brown adipocytes differentiation in vitro. Moreover, Bcl2l13 disruption dramatically inhibited the browning program of preadipocytes, evidenced by reduced Prdm16, Ucp1, Dio2 and Adrb3 expression. Our findings revealed that the inhibition effect of Bcl2l13 disruption on browning program may be independent of altering autophagy activity, but through regulating mitochondrial dynamic and biogenesis, supported by decreased mitochondrial fission/fussion genes, PGC-1α and mitochondrial respiratory chain complexes expression. Taken together, our study uncovered a novel function of Bcl2l13 in adipocytes differentiation and promoting browning program.
Bcl2l13 是 Bcl-2 家族的一员,最近有研究报道其作为 Atg32 的功能哺乳动物同源物,在调节细胞凋亡中发挥核心作用。然而,Bcl2l13 在脂肪组织中的作用尚未被研究。在本研究中,我们发现 Bcl2l13 的表达在冷暴露或β3-肾上腺素能激动剂 CL-316,243 刺激的白色脂肪组织棕色化过程中以及在体外棕色脂肪细胞分化过程中均增加。此外,Bcl2l13 的缺失显著抑制了前脂肪细胞的棕色化程序,表现为 Prdm16、Ucp1、Dio2 和 Adrb3 表达减少。我们的研究结果表明,Bcl2l13 缺失对棕色化程序的抑制作用可能不依赖于改变自噬活性,而是通过调节线粒体的动态和生物发生,减少线粒体分裂/融合基因、PGC-1α 和线粒体呼吸链复合物的表达来实现。总之,我们的研究揭示了 Bcl2l13 在脂肪细胞分化和促进棕色化程序中的新功能。