2. Academic Validation
  3. Creatine kinase B controls futile creatine cycling in thermogenic fat

Creatine kinase B controls futile creatine cycling in thermogenic fat

  • Nature. 2021 Feb;590(7846):480-485. doi: 10.1038/s41586-021-03221-y.
Janane F Rahbani 1 2,  Anna Roesler 1 2,  Mohammed F Hussain 1 2,  Bozena Samborska 1 2,  Christien B Dykstra 1 2,  Linus Tsai 3,  Mark P Jedrychowski 4,  Laurent Vergnes 5,  Karen Reue 5,  Bruce M Spiegelman 4,  Lawrence Kazak 6 7
Affiliations

Affiliations

  • 1 Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
  • 2 Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • 3 Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • 4 Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • 5 Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • 6 Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada. lawrence.kazak@mcgill.ca.
  • 7 Department of Biochemistry, McGill University, Montreal, Quebec, Canada. lawrence.kazak@mcgill.ca.
PMID: 33597756 DOI: 10.1038/s41586-021-03221-y
Abstract

Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and Cardiovascular Disease1. Thermogenesis by adipocytes can counteract obesity and metabolic diseases2,3. In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP-purportedly via a phosphorylation cycle4-to drive thermogenic respiration. However, the proteins that control this futile creatine cycle are unknown. Here we show that creatine kinase B (CKB) is indispensable for thermogenesis resulting from the futile creatine cycle, during which it traffics to mitochondria using an internal mitochondrial targeting sequence. CKB is powerfully induced by thermogenic stimuli in both mouse and human adipocytes. Adipocyte-selective inactivation of Ckb in mice diminishes thermogenic capacity, increases predisposition to obesity, and disrupts glucose homeostasis. CKB is therefore a key effector of the futile creatine cycle.

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