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 |
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| Authors: | Takeo Sakoguchi Masahisa Horiuchi Akihiro Asakawa Miharu Ushikai Goichiro Yoshida Mineko Fujimiya Ikuo Kato Masamitsu Nakazato Toru Takeuchi Takeyori Saheki Akio Inui |
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| Affiliation: | 1. Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;2. Department of Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;3. Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;4. Department of Health Science, National Institute of Fitness and Sports in Kanoya, Kanoya 891-2393, Japan;5. Department of Anatomy, Sapporo Medical University, Sapporo 060-8556, Japan;6. Department of Bioorganic Chemistry, Hokuriku University, Kanazawa 920-1181, Japan;7. Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692, Japan;8. Institute for Health Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan |
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| Abstract: | 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. |
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