Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
Nat Commun. 2022 Dec 12;13(1):7439. doi: 10.1038/s41467-022-35219-z.
Brown adipose tissue plays a central role in the regulation of the energy balance by expending energy to produce heat. NAD-dependent deacylase sirtuins have widely been recognized as positive regulators of brown adipose tissue thermogenesis. However, here we reveal that SIRT7, one of seven mammalian sirtuins, suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions. Whole-body and brown adipose tissue-specific Sirt7 knockout mice have higher body temperature and energy expenditure. SIRT7 deficiency increases the protein level of UCP1, a key regulator of brown adipose tissue thermogenesis. Mechanistically, we found that SIRT7 deacetylates insulin-like growth factor 2 mRNA-binding protein 2, an RNA-binding protein that inhibits the translation of Ucp1 mRNA, thereby enhancing its inhibitory action on Ucp1. Furthermore, SIRT7 attenuates the expression of batokine genes, such as fibroblast growth factor 21. In conclusion, we propose that SIRT7 serves as an energy-saving factor by suppressing brown adipose tissue functions.
棕色脂肪组织通过消耗能量产生热量来调节能量平衡，在这一过程中发挥着核心作用。NAD 依赖性脱酰基酶 sirtuins 已被广泛认为是棕色脂肪组织产热的正向调节因子。然而，在这里我们揭示了，作为七种哺乳动物 sirtuins 之一的 SIRT7 通过调节棕色脂肪组织的功能来抑制能量消耗和产热。全身性和棕色脂肪组织特异性的 Sirt7 敲除小鼠具有更高的体温和能量消耗。SIRT7 缺乏会增加 UCP1 的蛋白水平，UCP1 是棕色脂肪组织产热的关键调节因子。在机制上，我们发现 SIRT7 去乙酰化胰岛素样生长因子 2 mRNA 结合蛋白 2（一种抑制 Ucp1 mRNA 翻译的 RNA 结合蛋白），从而增强其对 Ucp1 的抑制作用。此外，SIRT7 还减弱了 batokine 基因（如成纤维细胞生长因子 21）的表达。总之，我们提出 SIRT7 通过抑制棕色脂肪组织的功能来充当节能因子。
