Institute of Food Nutrition and Health and Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH), 8603 Schwerzenbach, Switzerland.
Institute of Food Nutrition and Health and Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH), 8603 Schwerzenbach, Switzerland.
Cell Rep. 2020 Mar 10;30(10):3424-3433.e4. doi: 10.1016/j.celrep.2020.02.055.
UCP1-dependent thermogenesis is studied to define new strategies to ameliorate obesity and type 2 diabetes; however, animal models are mostly limited to germline mutations of UCP1, which can effect adaptive changes in UCP1-independent pathways. We develop an inducible mouse model for the sequential ablation of UCP1 brown and brite/beige adipocytes in adult mice. We demonstrate that activated brown adipocytes can increase systemic energy expenditure (EE) by 30%, while the contribution of brite/beige UCP1 cells is <5%. Notably, UCP1 adipocytes do not contribute to circulating FGF21 levels, either at room temperature or after cold exposure. We demonstrate that the FGF21-mediated effects on EE and glucose homeostasis are partially dependent on the presence of UCP1 cells, while the effect on weight loss is not. In conclusion, acute UCP1 cell deletion may be a useful model to study the impact of brown and brite/beige adipocytes on metabolism.
UCP1 依赖性产热被研究以定义改善肥胖和 2 型糖尿病的新策略；然而，动物模型主要限于 UCP1 的种系突变，这可能会影响 UCP1 非依赖性途径的适应性变化。我们开发了一种诱导型小鼠模型，用于在成年小鼠中顺序消融 UCP1 棕色和米色/beige 脂肪细胞。我们证明激活的棕色脂肪细胞可以使全身能量消耗 (EE) 增加 30%，而米色/beige UCP1 细胞的贡献<5%。值得注意的是，UCP1 脂肪细胞既不会在室温下也不会在冷暴露后对循环 FGF21 水平产生影响。我们证明，FGF21 对 EE 和葡萄糖稳态的影响部分依赖于 UCP1 细胞的存在，而对体重减轻的影响则不是。总之，急性 UCP1 细胞缺失可能是研究棕色和米色/beige 脂肪细胞对代谢影响的有用模型。
