Failure of the feeding response to fasting in carnitine-deficient juvenile visceral steatosis (JVS) mice: involvement of defective acyl-ghrelin secretion and enhanced corticotropin-releasing factor signaling in the hypothalamus.
Carnitine-deficient juvenile visceral steatosis (JVS) mice, suffering from fatty acid metabolism abnormalities, have reduced locomotor activity after fasting. We examined whether JVS mice exhibit specific defect in the feeding response to fasting, a key process of anti-famine homeostatic mechanism. Carnitine-deficient JVS mice showed grossly defective feeding response to 24 h-fasting, with almost no food intake in the first 4 h, in marked contrast to control animals. JVS mice also showed defective acyl-ghrelin response to fasting, less suppressed leptin, and seemingly normal corticotropin-releasing factor (CRF) expression in the hypothalamus despite markedly increased plasma corticosterone. The anorectic response was ameliorated by intraperitoneal administration of carnitine or acyl-ghrelin, with decreased CRF expression. Intracerebroventricular treatment of CRF type 2 receptor antagonist, anti-sauvagine-30, recovered the defective feeding response of 24 h-fasted JVS mice. The defective feeding response to fasting in carnitine-deficient JVS mice is due to the defective acyl-ghrelin and enhanced CRF signaling in the hypothalamus through fatty acid metabolism abnormalities. In this animal model, carnitine normalizes the feeding response through an inhibition of CRF.
Sakoguchi
Takeo
T
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Horiuchi
Masahisa
M
Asakawa
Akihiro
A
Ushikai
Miharu
M
Yoshida
Goichiro
G
Fujimiya
Mineko
M
Kato
Ikuo
I
Nakazato
Masamitsu
M
Takeuchi
Toru
T
Saheki
Takeyori
T
Inui
Akio
A
D000818:Animals; D002331:Carnitine / Q000172:deficiency*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004195:Disease Models, Animal; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005247:Feeding Behavior; D054439:Ghrelin / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism
C101531:CRF receptor type 2; D005227:Fatty Acids; D054439:Ghrelin; D020738:Leptin; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D002331:Carnitine