Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.

<h4>Aims</h4>Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect...

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Autores principales:	Vanlata Patel, Raghu Adya, Jing Chen, Manjunath Ramanjaneya, Muhammad F Bari, Sunil K Bhudia, Edward W Hillhouse, Bee K Tan, Harpal S Randeva
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e31b47f830c4c7d9cea277508f5121a
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spelling	oai:doaj.org-article:1e31b47f830c4c7d9cea277508f5121a2021-11-18T08:34:19ZNovel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.1932-620310.1371/journal.pone.0087102https://doaj.org/article/1e31b47f830c4c7d9cea277508f5121a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24498293/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia.<h4>Methods and results</h4>FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased.<h4>Conclusion</h4>In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia.Vanlata PatelRaghu AdyaJing ChenManjunath RamanjaneyaMuhammad F BariSunil K BhudiaEdward W HillhouseBee K TanHarpal S RandevaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87102 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vanlata Patel Raghu Adya Jing Chen Manjunath Ramanjaneya Muhammad F Bari Sunil K Bhudia Edward W Hillhouse Bee K Tan Harpal S Randeva Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
description	<h4>Aims</h4>Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia.<h4>Methods and results</h4>FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased.<h4>Conclusion</h4>In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia.
format	article
author	Vanlata Patel Raghu Adya Jing Chen Manjunath Ramanjaneya Muhammad F Bari Sunil K Bhudia Edward W Hillhouse Bee K Tan Harpal S Randeva
author_facet	Vanlata Patel Raghu Adya Jing Chen Manjunath Ramanjaneya Muhammad F Bari Sunil K Bhudia Edward W Hillhouse Bee K Tan Harpal S Randeva
author_sort	Vanlata Patel
title	Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
title_short	Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
title_full	Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
title_fullStr	Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
title_full_unstemmed	Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
title_sort	novel insights into the cardio-protective effects of fgf21 in lean and obese rat hearts.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1e31b47f830c4c7d9cea277508f5121a
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Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.

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