Ghrelin Induces Time-Dependent Modulation of Thermoregulation in the Cold

Abstract

Fasted mice show torpor-like hypothermia in the cold in their inactive phase. The aim of the present study was to elucidate whether leptin and/or ghrelin are involved in this reaction and to identify its neurophysiological mechanisms. In ob/ob mice, which lack leptin, metabolic heat production (oxygen consumption, Vo₂) was suppressed in 20°C cold in both the light and dark phases, resulting in hypothermia. When wild-type mice received a systemic injection of 8 µg ghrelin in the early light phase, followed by a 2-h cold exposure to 10°C, their core body temperature (T_b) decreased by 1.7°C, and they displayed a less marked increase in Vo₂ compared with vehicle-injected mice. However, ghrelin injection in the early dark phase resulted in the maintenance of T_b and increased Vo₂ in the mice, which was similar to the result observed in the vehicle-injected mice. The number of doubly labeled neurons with cFos and neuropeptide Y (NPY) in the suprachiasmatic nucleus was greater in the light phase in the ghrelin-injected mice, which may suggest that ghrelin activates NPY neurons. On the contrary, in the paraventricular nucleus, the counts became greater only when they were exposed to the cold in the dark phase. These results indicate that ghrelin plays an important role in inducing time-dependent changes in thermoregulation in the cold via hypothalamic pathways. (Author correspondence: [email protected])

Keywords:

• Body temperature
• Circadian rhythm
• Food deprivation
• Ghrelin
• Hypothalamus
• Metabolism

ACKNOWLEDGEMENTS

The present study was partly supported by KAKENHI Nos. 17390062 and 20790195 from the Japan Society for the Promotion of Science and Sport Sciences for the Promotion of Active Life, Waseda University Global COE Program, and MEXT KIBANKEISEI (2010).

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.