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 C. Chua, Jr.

Research output: Contribution to journalArticle

59 Citations (Scopus)

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 2014

Fingerprint

Insulin Resistance
Neurons
Glucose
Obesity
Fibroblast Growth Factors
Genetic Models
High Fat Diet
Leptin
Hypoglycemic Agents
Hyperglycemia
Type 2 Diabetes Mellitus
Therapeutics
Central Nervous System
Hormones
Insulin
Morbidity
Mortality

Keywords

  • AGRP/NPY neurons
  • Diabetes
  • FGF19
  • Obesity

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. / Marcelin, Geneviève; Jo, Young-Hwan; Li, Xiaosong; Schwartz, Gary J.; Zhang, Ying; Dun, Nae J.; Lyu, Rong Ming; Blouet, Clémence; Chang, Jaw K.; Chua, Jr., Streamson C.

In: Molecular Metabolism, Vol. 3, No. 1, 02.2014, p. 19-28.

Research output: Contribution to journalArticle

Marcelin, Geneviève ; Jo, Young-Hwan ; Li, Xiaosong ; Schwartz, Gary J. ; Zhang, Ying ; Dun, Nae J. ; Lyu, Rong Ming ; Blouet, Clémence ; Chang, Jaw K. ; Chua, Jr., Streamson C. / Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. In: Molecular Metabolism. 2014 ; Vol. 3, No. 1. pp. 19-28.
@article{5bf895efdfc242d1b48c61991f370808,
title = "Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism",
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.",
keywords = "AGRP/NPY neurons, Diabetes, FGF19, Obesity",
author = "Genevi{\`e}ve Marcelin and Young-Hwan Jo and Xiaosong Li and Schwartz, {Gary J.} and Ying Zhang and Dun, {Nae J.} and Lyu, {Rong Ming} and Cl{\'e}mence Blouet and Chang, {Jaw K.} and {Chua, Jr.}, {Streamson C.}",
year = "2014",
month = "2",
doi = "10.1016/j.molmet.2013.10.002",
language = "English (US)",
volume = "3",
pages = "19--28",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier GmbH",
number = "1",

}

TY - JOUR

T1 - Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism

AU - Marcelin, Geneviève

AU - Jo, Young-Hwan

AU - Li, Xiaosong

AU - Schwartz, Gary J.

AU - Zhang, Ying

AU - Dun, Nae J.

AU - Lyu, Rong Ming

AU - Blouet, Clémence

AU - Chang, Jaw K.

AU - Chua, Jr., Streamson C.

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

KW - AGRP/NPY neurons

KW - Diabetes

KW - FGF19

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=84893411706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893411706&partnerID=8YFLogxK

U2 - 10.1016/j.molmet.2013.10.002

DO - 10.1016/j.molmet.2013.10.002

M3 - Article

AN - SCOPUS:84893411706

VL - 3

SP - 19

EP - 28

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

IS - 1

ER -