Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis

Abstract Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Khadija M. Alawi, David Tandio, Jin Xu, Pratish Thakore, Georgia Papacleovoulou, Elizabeth S. Fernandes, Cristina Legido-Quigley, Catherine Williamson, Susan D. Brain
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50ebdd5ef16b4a1fac47e63d32bcb9e7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:50ebdd5ef16b4a1fac47e63d32bcb9e7
record_format	dspace
spelling	oai:doaj.org-article:50ebdd5ef16b4a1fac47e63d32bcb9e72021-12-02T15:18:52ZTransient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis10.1038/s41598-017-02439-z2045-2322https://doaj.org/article/50ebdd5ef16b4a1fac47e63d32bcb9e72017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02439-zhttps://doaj.org/toc/2045-2322Abstract Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in liver disease, including lysophosphatidylcholine (LPC). Cholestasis is characterized by impairment of excretion of bile acids, leading to elevation of hepatic bile acids. We investigated the contribution of TRPC5 in a murine model of cholestasis. Wild-type (WT) and TRPC5 knock-out (KO) mice were fed a diet supplemented with 0.5% cholic acid (CA) for 21 days. CA-diet supplementation resulted in enlargement of the liver in WT mice, which was ameliorated in TRPC5 KO mice. Hepatic bile acid and lipid content was elevated in WT mice, with a reduction observed in TRPC5 KO mice. Consistently, liver enzymes were significantly increased in cholestatic WT mice and significantly blunted in TRPC5 KO mice. Localized dyslipidaemia, secondary to cholestasis, was investigated utilizing a selected lipid analysis. This revealed significant perturbations in the lipid profile following CA-diet feeding, with increased cholesterol, triglycerides and phospholipids, in WT, but not TRPC5 KO mice. Our results suggest that activation of TRPC5 contributes to the development of cholestasis and associated dyslipidemia. Modulation of TRPC5 activity may present as a novel therapeutic target for liver disease.Khadija M. AlawiDavid TandioJin XuPratish ThakoreGeorgia PapacleovoulouElizabeth S. FernandesCristina Legido-QuigleyCatherine WilliamsonSusan D. BrainNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Khadija M. Alawi David Tandio Jin Xu Pratish Thakore Georgia Papacleovoulou Elizabeth S. Fernandes Cristina Legido-Quigley Catherine Williamson Susan D. Brain Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
description	Abstract Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in liver disease, including lysophosphatidylcholine (LPC). Cholestasis is characterized by impairment of excretion of bile acids, leading to elevation of hepatic bile acids. We investigated the contribution of TRPC5 in a murine model of cholestasis. Wild-type (WT) and TRPC5 knock-out (KO) mice were fed a diet supplemented with 0.5% cholic acid (CA) for 21 days. CA-diet supplementation resulted in enlargement of the liver in WT mice, which was ameliorated in TRPC5 KO mice. Hepatic bile acid and lipid content was elevated in WT mice, with a reduction observed in TRPC5 KO mice. Consistently, liver enzymes were significantly increased in cholestatic WT mice and significantly blunted in TRPC5 KO mice. Localized dyslipidaemia, secondary to cholestasis, was investigated utilizing a selected lipid analysis. This revealed significant perturbations in the lipid profile following CA-diet feeding, with increased cholesterol, triglycerides and phospholipids, in WT, but not TRPC5 KO mice. Our results suggest that activation of TRPC5 contributes to the development of cholestasis and associated dyslipidemia. Modulation of TRPC5 activity may present as a novel therapeutic target for liver disease.
format	article
author	Khadija M. Alawi David Tandio Jin Xu Pratish Thakore Georgia Papacleovoulou Elizabeth S. Fernandes Cristina Legido-Quigley Catherine Williamson Susan D. Brain
author_facet	Khadija M. Alawi David Tandio Jin Xu Pratish Thakore Georgia Papacleovoulou Elizabeth S. Fernandes Cristina Legido-Quigley Catherine Williamson Susan D. Brain
author_sort	Khadija M. Alawi
title	Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
title_short	Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
title_full	Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
title_fullStr	Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
title_full_unstemmed	Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
title_sort	transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/50ebdd5ef16b4a1fac47e63d32bcb9e7
work_keys_str_mv	AT khadijamalawi transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT davidtandio transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT jinxu transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT pratishthakore transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT georgiapapacleovoulou transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT elizabethsfernandes transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT cristinalegidoquigley transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT catherinewilliamson transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis AT susandbrain transientreceptorpotentialcanonical5channelsplaysanessentialroleinhepaticdyslipidemiaassociatedwithcholestasis
_version_	1718387444757299200

Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis

Ejemplares similares