Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism

Geneviève Marcelin, Young Hwan Jo, Xiaosong Li, Gary J. Schwartz, Ying Zhang, Nae J. Dun, Rong Ming Lyu, Clémence Blouet, Jaw K. Chang, Streamson Chua

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Tight control of glucose excursions has been a long-standing goal of treatment for patients with type 2 diabetes mellitus in order to ameliorate the morbidity and mortality associated with hyperglycemia. Fibroblast growth factor (FGF) 19 is a hormone-like enterokine released postprandially that emerged as a potential therapeutic agent for metabolic disorders, including diabetes and obesity. Remarkably, FGF19 treatment has hypoglycemic actions that remain potent in models of genetic and acquired insulin resistance. Here, we provided evidence that the central nervous system responds to FGF19 administered in the periphery. Then, in two mouse models of insulin resistance, leptin-deficiency and high-fat diet feeding, third intra-cerebro-ventricular infusions of FGF19 improved glycemic status, reduced insulin resistance and potentiated insulin signaling in the periphery. In addition, our study highlights a new mechanism of central FGF19 action, involving the suppression of AGRP/NPY neuronal activity. Overall, our work unveils novel regulatory pathways induced by FGF19 that will be useful in the design of novel strategies to control diabetes in obesity.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalMolecular Metabolism
Volume3
Issue number1
DOIs
StatePublished - Feb 1 2014

Keywords

  • AGRP/NPY neurons
  • Diabetes
  • FGF19
  • Obesity

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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