That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking from birth (germline ). However, germline mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective disruption. We find that, although germline mice succumb to cold-induced hypothermia with complete penetrance, most mice with the inducible deletion of maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of and creatine kinase b (, an effector of UCP1-independent thermogenesis) exacerbates cold intolerance. Following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature brown adipocytes that coordinately restore UCP1 and CKB expression. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy—through UCP1 and CKB—to promote cold-induced energy dissipation.

中文翻译：

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UCP1 和 CKB 对冷触发脂肪细胞产热的并行控制

解偶联蛋白 1 (UCP1) 是脂肪细胞产热的唯一介体，这是一种传统观点，主要是从出生时基因缺乏的小鼠（种系）生热输出的衰减推断出来的。然而，种系小鼠的棕色脂肪组织内存在继发性变化。为了减轻这些潜在的令人困惑的辅助变化，我们构建了具有诱导性脂肪细胞选择性破坏的小鼠。我们发现，尽管种系小鼠完全外显地死于寒冷诱导的低温，但大多数具有诱导性缺失的小鼠在寒冷中仍能保持恒温。然而，诱导性脂肪细胞选择性共缺失肌酸激酶 b（UCP1 独立生热作用的效应物）会加剧寒冷不耐受。成熟脂肪细胞中 UCP1 缺失或 UCP1/CKB 共缺失后，适度的冷暴露会触发成熟棕色脂肪细胞的再生，从而协调恢复 UCP1 和 CKB 的表达。我们的研究结果表明，产热脂肪细胞通过 UCP1 和 CKB 利用非旁系同源蛋白质冗余来促进冷诱导的能量耗散。