Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice

Abstract

We found reduced locomotor activity (LA) under fasting in systemic carnitine-deficient juvenile visceral steatosis ( jvs −/−) mice. When food was withdrawn at 8:00 a.m. (lights-off at 7:00 p.m., 12 h/cycle), the nocturnal LA of jvs −/− mice was much less than the control ( jvs +/+ and jvs +/−) mice. LA recovered under carnitine or sucrose administration, but not under medium-chain triglyceride. In addition, fasted jvs −/− mice, without any energy supply, were activated by modafinil, a stimulator of the dopamine pathway. These results suggest that the reduced LA is not adequately explained by energy deficit. As the fasted jvs −/− mice showed lower body core temperature (BT), we examined the central nervous system regulating LA and BT. We found lower percentage of c-Fos positive orexin neurons in the lateral hypothalamus and reduced orexin-A concentration in the cerebrospinal fluid of fasted jvs −/− mice. Sleep analysis revealed that fasted jvs −/− mice had disruption of prolonged wakefulness, with a higher frequency of brief episodes of non-REM sleep during the dark period than fasted jvs +/+ mice. These results strongly suggest that the reduced LA in fasted jvs −/− mice is related to the inhibition of orexin neuronal activity.