College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Int J Mol Sci. 2024 Sep 29;25(19):10514. doi: 10.3390/ijms251910514.
Sirtuin 5 (SIRT5) plays an important role in the maintenance of lipid metabolism and in white adipose tissue browning. In this study, we established a mouse model for diet-induced obesity and the browning of white fat; combined with gene expression intervention, transcriptome sequencing, and cell molecular biology methods, the regulation and molecular mechanisms of SIRT5 on fat deposition and beige fat formation were studied. The results showed that the loss of SIRT5 in obese mice exacerbated white adipose tissue deposition and metabolic inflexibility. Furthermore, the deletion of SIRT5 in a white-fat-browning mouse increased the succinylation of uncoupling protein 1 (UCP1), resulting in a loss of the beiging capacity of the subcutaneous white adipose tissue and impaired cold tolerance. Mechanistically, the inhibition of SIRT5 results in impaired CCAAT/enhancer binding protein beta (C/EBPβ) expression in brown adipocytes, which in turn reduces the UCP1 transcriptional pathway. Thus, the transcription of UCP1 mediated by the SIRT5-C/EBPβ axis is critical in regulating energy balance and obesity-related metabolism.
Sirtuin 5（SIRT5）在维持脂质代谢和白色脂肪组织棕色化中发挥重要作用。在这项研究中，我们建立了饮食诱导肥胖和白色脂肪棕色化的小鼠模型；结合基因表达干预、转录组测序和细胞分子生物学方法，研究了 SIRT5 对脂肪沉积和米色脂肪形成的调节和分子机制。结果表明，肥胖小鼠中 SIRT5 的缺失加剧了白色脂肪组织的沉积和代谢灵活性的丧失。此外，在白色脂肪棕色化小鼠中敲除 SIRT5 会增加解偶联蛋白 1（UCP1）的琥珀酰化，导致皮下白色脂肪组织的褐色化能力丧失和耐寒性受损。在机制上，棕色脂肪细胞中 SIRT5 的抑制导致 CCAAT/增强子结合蛋白 β（C/EBPβ）的表达受损，进而减少 UCP1 的转录途径。因此，SIRT5-C/EBPβ 轴介导的 UCP1 转录对于调节能量平衡和肥胖相关代谢至关重要。
