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Article: FGF21 Maintains Glucose Homeostasis by Mediating the Cross Talk Between Liver and Brain During Prolonged Fasting

TitleFGF21 Maintains Glucose Homeostasis by Mediating the Cross Talk Between Liver and Brain During Prolonged Fasting
Authors
Issue Date2014
Citation
Diabetes, 2014, v. 63 n. 12, p. 4064-4075 How to Cite?
AbstractHepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain.
Persistent Identifierhttp://hdl.handle.net/10722/203056
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185

 

DC FieldValueLanguage
dc.contributor.authorLiang, Qen_US
dc.contributor.authorZhong, Len_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorBornstein, SRen_US
dc.contributor.authorHong, Den_US
dc.contributor.authorTriggle, Cen_US
dc.contributor.authorXu, Aen_US
dc.date.accessioned2014-09-19T11:29:23Z-
dc.date.available2014-09-19T11:29:23Z-
dc.date.issued2014en_US
dc.identifier.citationDiabetes, 2014, v. 63 n. 12, p. 4064-4075en_US
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/203056-
dc.description.abstractHepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain.en_US
dc.languageengen_US
dc.relation.ispartofDiabetesen_US
dc.titleFGF21 Maintains Glucose Homeostasis by Mediating the Cross Talk Between Liver and Brain During Prolonged Fastingen_US
dc.typeArticleen_US
dc.identifier.emailLiang, Q: larry10@hku.hken_US
dc.identifier.emailZhong, L: kelsey@hku.hken_US
dc.identifier.emailZhang, J: hjzhang@hkucc.hku.hken_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_US
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_US
dc.identifier.authorityWang, Y=rp00239en_US
dc.identifier.authorityXu, A=rp00485en_US
dc.identifier.doi10.2337/db14-0541en_US
dc.identifier.hkuros235336en_US

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