title: Paraventricular NUCB2/nesfatin-1 is directly targeted by leptin and mediates its anorexigenic effect.
abstract: An adipokine leptin plays a central role in the regulation of feeding and energy homeostasis via acting on the hypothalamus. However, its downstream neuronal mechanism is not thoroughly understood. The neurons expressing nucleobindin-2 (NUCB2)-derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) have been implicated in feeding and energy homeostasis. The present study aimed to explore the role of PVN NUCB2/nesfatin-1 in the leptin action, by using adeno-associated virus (AAV) vectors encoding shRNA targeting NUCB2 (AAV-NUCB2-shRNA). Leptin directly interacted and increased cytosolic Ca(2+) in single neurons isolated from the PVN, predominantly in NUCB2/nesftin-1-immunoreactive neurons. Treatment with leptin in vivo and in vitro markedly increased NUCB2 mRNA expression in the PVN. Peripheral and central injections of leptin failed to significantly inhibit food intake in mice receiving AAV-NUCB2. These results indicate that PVN NUCB2/nesfatin-1 is directly targeted by leptin, and mediates its anorexigenic effect.
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Gantulga
authors.initials: G
authors.lastname: Darambazar
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: EnXu
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Atsumi
authors.initials: A
authors.lastname: Shinozaki
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Motoshima
authors.affiliation: Kitakanto Molecular Novel Research Institute for Obesity and Metabolism, Midori, Gunma 379-2311, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Developmental Physiology, Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan. Electronic address: tyada@jichi.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006706:Homeostasis / Q000187:drug effects; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D000080866:Nucleobindins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: Feeding; Leptin; Nesfatin-1; Paraventricular nucleus