Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB

Document Type

Article

Publication Date

3-5-2024

Institution/Department

MaineHealth Institute for Research, Center for Molecular Medicine

Journal Title

Cell metabolism

MeSH Headings

Animals; Mice; Adipocytes, Brown (metabolism); Adipose Tissue, Brown (metabolism); Thermogenesis; Uncoupling Protein 1 (genetics, metabolism); Creatine Kinase, BB Form (metabolism)

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.

First Page

526

Last Page

540.e7

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