title: N-methyl-d-aspartate receptor coagonist d-serine suppresses intake of high-preference food.
abstract: d-Serine is abundant in the forebrain and physiologically important for modulating excitatory glutamatergic neurotransmission as a coagonist of synaptic N-methyl-d-aspartate (NMDA) receptor. NMDA signaling has been implicated in the control of food intake. However, the role of d-serine on appetite regulation is unknown. To clarify the effects of d-serine on appetite, we investigated the effect of oral d-serine ingestion on food intake in three different feeding paradigms (one-food access, two-food choice, and refeeding after 24-h fasting) using three different strains of male mice (C57Bl/6J, BKS, and ICR). The effect of d-serine was also tested in leptin signaling-deficient db/db mice and sensory-deafferented (capsaicin-treated) mice. The expression of orexigenic neuropeptides [neuropeptide Y (Npy) and agouti-related protein (Agrp)] in the hypothalamus was compared in fast/refed experiments. Conditioned taste aversion for high-fat diet (HFD) was tested in the d-serine-treated mice. Under the one-food-access paradigm, some of the d-serine-treated mice showed starvation, but not when fed normal chow. HFD feeding with d-serine ingestion did not cause aversion. Under the two-food-choice paradigm, d-serine suppressed the intake of high-preference food but not normal chow. d-Serine also effectively suppressed HFD intake but not normal chow in db/db mice and sensory-deafferented mice. In addition, d-serine suppressed normal chow intake after 24-h fasting despite higher orexigenic gene expression in the hypothalamus. d-Serine failed to suppress HFD intake in the presence of L-701,324, the selective and full antagonist at the glycine-binding site of the NMDA receptor. Therefore, d-serine suppresses the intake of high-preference food through coagonism toward NMDA receptors.
authors.affiliation: Laboratory of Metabolic Signal, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan; tsutomus@gunma-u.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Psychiatry, School of Medicine, Shinshu University, Matsumoto, Nagano, Japan;
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Laboratory of Metabolic Signal, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan;
authors.forename: Sho
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Research Center for Human and Environmental Sciences, Shinshu University, Matsumoto, Nagano, Japan;
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.affiliation: Laboratory of Metabolic Signal, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan;
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yokota-Hashimoto
authors.affiliation: Department of Psychiatry, School of Medicine, Shinshu University, Matsumoto, Nagano, Japan;
authors.forename: Kuni
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Division of Integrated Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan; and.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Kitasato University, Tokyo, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Division of Integrated Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan; and.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
authors.affiliation: Department of Psychiatry, School of Medicine, Shinshu University, Matsumoto, Nagano, Japan;
authors.forename: Naoji
authors.initials: N
authors.lastname: Amano
authors.affiliation: Laboratory of Metabolic Signal, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan;
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D002755:Choice Behavior; D003213:Conditioning, Psychological; D059305:Diet, High-Fat; D015536:Down-Regulation; D004435:Eating / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009478:Neuropeptide Y / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism; D018689:Sensory System Agents; D012694:Serine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D001067:Appetite Depressants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009478:Neuropeptide Y; D016194:Receptors, N-Methyl-D-Aspartate; D018689:Sensory System Agents; D012694:Serine
keywords: anorexia; food preference