1. Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB.
- Author
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Rahbani, Janane F., Bunk, Jakub, Lagarde, Damien, Samborska, Bozena, Roesler, Anna, Xiao, Haopeng, Shaw, Abhirup, Kaiser, Zafir, Braun, Jessica L., Geromella, Mia S., Fajardo, Val A., Koza, Robert A., and Kazak, Lawrence
- Abstract
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 Ucp1 from birth (germline Ucp1
−/− ). However, germline Ucp1−/− mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption. We find that, although germline Ucp1−/− mice succumb to cold-induced hypothermia with complete penetrance, most mice with the inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase b (Ckb , 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. [Display omitted] • Inducible adipocyte-specific Ucp1 deletion evades secondary changes beyond UCP1 • Individually, UCP1 and CKB are dispensable for cold-stimulated thermogenesis • UCP1 and CKB co-deletion causes hypothermia with near-full penetrance • Quantitative contribution of UCP1-independent adipocyte thermogenesis is defined Rahbani and Bunk et al. reveal that thermogenic adipocytes utilize UCP1 and CKB in parallel to support whole-body thermogenic demand in response to acute cold exposure. [ABSTRACT FROM AUTHOR]- Published
- 2024
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