Mice lacking brain-type creatine kinase activity show defective thermoregulation

Femke Streijger, Helma Pluk, Frank Oerlemans, Gaby Beckers, Antonio C. Bianco, Miriam O. Ribeiro, Bé Wieringa, Catharina E.E.M. Van der Zee

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~ 1.0 °C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK- -/- - mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK- -/- - mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalPhysiology AND Behavior
Volume97
Issue number1
DOIs
StatePublished - Apr 20 2009

Keywords

  • Brown adipose tissue
  • Creatine kinase
  • Creatine kinase double knockout mice
  • Thermogenic activity
  • UCP1 mRNA
  • White adipose tissue

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Experimental and Cognitive Psychology

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