Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states

Putra Santoso, Masanori Nakata, Kazuhiro Shiizaki, Zhang Boyang, Kumari Parmila, Zesemdorj Otgon-Uul, Koshi Hashimoto, Tetsurou Satoh, Masatomo Mori, Makoto Kuro-O, Toshihiko Yada

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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 [Ca 2+ ] i in 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.

Original languageEnglish (US)
Article number45819
JournalScientific reports
Volume7
DOIs
StatePublished - Apr 4 2017

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    Santoso, P., Nakata, M., Shiizaki, K., Boyang, Z., Parmila, K., Otgon-Uul, Z., Hashimoto, K., Satoh, T., Mori, M., Kuro-O, M., & Yada, T. (2017). Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states. Scientific reports, 7, [45819]. https://doi.org/10.1038/srep45819