title: Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states.
abstract: Fibroblast growth factor 21 (FGF21), liver-derived hormone, exerts diverse metabolic effects, being considered for clinical application to treat obesity and diabetes. However, its anorexigenic effect is debatable and whether it involves the central mechanism remains unclarified. Moreover, the neuron mediating FGF21's anorexigenic effect and the systemic energy state supporting it are unclear. We explored the target neuron and fed/fasted state dependence of FGF21's anorexigenic action. Intracerebroventricular (ICV) injection of FGF21 markedly suppressed food intake in fed mice with elevated blood glucose. FGF21 induced c-Fos expression preferentially in hypothalamic paraventricular nucleus (PVN), and increased mRNA expression selectively for nucleobindin 2/nesfatin-1 (NUCB2/Nesf-1). FGF21 at elevated glucose increased [Ca2+]iin PVN NUCB2/Nesf-1 neurons. FGF21 failed to suppress food intake in PVN-preferential Sim1-Nucb2-KO mice. These findings reveal that FGF21, assisted by elevated glucose, activates PVN NUCB2/Nesf-1 neurons to suppress feeding under fed states, serving as the glycemia-monitoring messenger of liver-hypothalamic network for integrative regulation of energy and glucose metabolism.
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Putra
authors.initials: P
authors.lastname: Santoso
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiizaki
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Boyang
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Kumari
authors.initials: K
authors.lastname: Parmila
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Zesemdorj
authors.initials: Z
authors.lastname: Otgon-Uul
authors.affiliation: Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.|Department of Preemptive Medicine and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.|Metabolic and Obese Research Institute, Maebashi, Gunma 371-0037, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.affiliation: Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuro-O
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004435:Eating; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D000080866:Nucleobindins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D012527:Satiation / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors