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

Autor:	Rahbani JF; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Bunk J; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada., Lagarde D; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Samborska B; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Roesler A; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada., Xiao H; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Shaw A; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Kaiser Z; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada., Braun JL; Department of Kinesiology, Brock University, St. Catharines, ON L2S 3A1, Canada., Geromella MS; Department of Kinesiology, Brock University, St. Catharines, ON L2S 3A1, Canada., Fajardo VA; Department of Kinesiology, Brock University, St. Catharines, ON L2S 3A1, Canada., Koza RA; MaineHealth Institute for Research, Scarborough, ME 04074, USA., Kazak L; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: lawrence.kazak@mcgill.ca.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2024 Mar 05; Vol. 36 (3), pp. 526-540.e7. Date of Electronic Publication: 2024 Jan 24.
DOI:	10.1016/j.cmet.2024.01.001
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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