Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice.
Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Masanori
M
Nakata
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Darambazar
D
Gantulga
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Putra
P
Santoso
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Boyang
B
Zhang
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Chiaki
C
Masuda
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Masatomo
M
Mori
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Takashi
T
Okada
Division of Integrative Physiology (M.N., D.G., P.S., B.Z., T.Y.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; Department of Biochemistry and Molecular Biology (C.M., T.O.), Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, Japan; Metabolic and Obese Research Institute (M.M.), Maebashi, Gunma 371-0037, Japan; and Department of Developmental Physiology (T.Y.), Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Toshihiko
T
Yada
D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002151:Calorimetry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D000080866:Nucleobindins; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014667:Vasopressins / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D034741:RNA, Small Interfering; D014667:Vasopressins; D010121:Oxytocin