TY - JOUR
T1 - Mice lacking brain-type creatine kinase activity show defective thermoregulation
AU - Streijger, Femke
AU - Pluk, Helma
AU - Oerlemans, Frank
AU - Beckers, Gaby
AU - Bianco, Antonio C.
AU - Ribeiro, Miriam O.
AU - Wieringa, Bé
AU - Van der Zee, Catharina E.E.M.
N1 - Funding Information:
This research is supported by a research grant from the Radboud University Nijmegen Medical Centre. We want to thank Huib Croes for paraffin histology and immunocytochemistry, Mietske Wijers for her contribution to the electron microscopy study, Dr. L. Brewster for the vasoconstriction pilot experiments and our colleagues in the Central Animal Facility for support and advice regarding the animal care.
PY - 2009/4/20
Y1 - 2009/4/20
N2 - 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.
AB - 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.
KW - Brown adipose tissue
KW - Creatine kinase
KW - Creatine kinase double knockout mice
KW - Thermogenic activity
KW - UCP1 mRNA
KW - White adipose tissue
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U2 - 10.1016/j.physbeh.2009.02.003
DO - 10.1016/j.physbeh.2009.02.003
M3 - Article
C2 - 19419668
AN - SCOPUS:62749117195
VL - 97
SP - 76
EP - 86
JO - Physiology and Behavior
JF - Physiology and Behavior
SN - 0031-9384
IS - 1
ER -