Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice.
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 When food was withdrawn at 8:00 a.m. (lights-off at 7:00 p.m., 12h/cycle), the nocturnal LA of jvs(-/-) mice was much less than the control (jvs(+/+) and jvs(+/-)) mice.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.
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Goichiro
G
Yoshida
Meng Xian
MX
Li
Masahisa
M
Horiuchi
Shiro
S
Nakagawa
Mie
M
Sakata
Satoshi
S
Kuchiiwa
Toshiko
T
Kuchiiwa
Md Abdul
MA
Jalil
Laila
L
Begum
Yao Bang
YB
Lu
Mikio
M
Iijima
Takeshi
T
Hanada
Masamitsu
M
Nakazato
Zhi-Li
ZL
Huang
Naomi
N
Eguchi
Keiko
K
Kobayashi
Takeyori
T
Saheki
D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002331:Carnitine / Q000008:administration & dosage / Q000172:deficiency*; D004569:Electroencephalography / Q000379:methods; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D017286:Polysomnography / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D013395:Sucrose; D005947:Glucose; D002331:Carnitine