The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two...

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Autores principales:	Timothy E. Thayer, Christian L. Lino Cardenas, Trejeeve Martyn, Christopher J. Nicholson, Lisa Traeger, Florian Wunderer, Charles Slocum, Haakon Sigurslid, Hannah R. Shakartzi, Caitlin O’Rourke, Georgia Shelton, Mary D. Buswell, Hanna Barnes, Leif R. Neitzel, Clara D. Ledsky, Jason Pingcheng Li, Megan F. Burke, Eric Farber-Eger, Daniel S. Perrien, Ravindra Kumar, Kathleen E. Corey, Quinn S. Wells, Kenneth D. Bloch, Charles C. Hong, Donald B. Bloch, Rajeev Malhotra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b2d4d623f694b79a8b273377b95590c
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spelling	oai:doaj.org-article:0b2d4d623f694b79a8b273377b95590c2021-12-02T17:40:44ZThe Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease10.1038/s41598-020-66770-82045-2322https://doaj.org/article/0b2d4d623f694b79a8b273377b95590c2020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66770-8https://doaj.org/toc/2045-2322Abstract Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two BMP inhibitors reduced hepatic triglyceride content in diabetic (db/db) mice. BMP inhibitor-induced decrease in hepatic triglyceride levels was associated with decreased mRNA encoding Dgat2, an enzyme integral to triglyceride synthesis. Treatment of hepatoma cells with BMP2 induced DGAT2 expression and activity via intracellular SMAD signaling. In humans we identified a rare missense single nucleotide polymorphism in the BMP type 1 receptor ALK6 (rs34970181;R371Q) associated with a 2.1-fold increase in the prevalence of NAFLD. In vitro analyses revealed R371Q:ALK6 is a previously unknown constitutively active receptor. These data show that BMP signaling is an important determinant of NAFLD in a murine model and is associated with NAFLD in humans.Timothy E. ThayerChristian L. Lino CardenasTrejeeve MartynChristopher J. NicholsonLisa TraegerFlorian WundererCharles SlocumHaakon SigurslidHannah R. ShakartziCaitlin O’RourkeGeorgia SheltonMary D. BuswellHanna BarnesLeif R. NeitzelClara D. LedskyJason Pingcheng LiMegan F. BurkeEric Farber-EgerDaniel S. PerrienRavindra KumarKathleen E. CoreyQuinn S. WellsKenneth D. BlochCharles C. HongDonald B. BlochRajeev MalhotraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Timothy E. Thayer Christian L. Lino Cardenas Trejeeve Martyn Christopher J. Nicholson Lisa Traeger Florian Wunderer Charles Slocum Haakon Sigurslid Hannah R. Shakartzi Caitlin O’Rourke Georgia Shelton Mary D. Buswell Hanna Barnes Leif R. Neitzel Clara D. Ledsky Jason Pingcheng Li Megan F. Burke Eric Farber-Eger Daniel S. Perrien Ravindra Kumar Kathleen E. Corey Quinn S. Wells Kenneth D. Bloch Charles C. Hong Donald B. Bloch Rajeev Malhotra The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
description	Abstract Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two BMP inhibitors reduced hepatic triglyceride content in diabetic (db/db) mice. BMP inhibitor-induced decrease in hepatic triglyceride levels was associated with decreased mRNA encoding Dgat2, an enzyme integral to triglyceride synthesis. Treatment of hepatoma cells with BMP2 induced DGAT2 expression and activity via intracellular SMAD signaling. In humans we identified a rare missense single nucleotide polymorphism in the BMP type 1 receptor ALK6 (rs34970181;R371Q) associated with a 2.1-fold increase in the prevalence of NAFLD. In vitro analyses revealed R371Q:ALK6 is a previously unknown constitutively active receptor. These data show that BMP signaling is an important determinant of NAFLD in a murine model and is associated with NAFLD in humans.
format	article
author	Timothy E. Thayer Christian L. Lino Cardenas Trejeeve Martyn Christopher J. Nicholson Lisa Traeger Florian Wunderer Charles Slocum Haakon Sigurslid Hannah R. Shakartzi Caitlin O’Rourke Georgia Shelton Mary D. Buswell Hanna Barnes Leif R. Neitzel Clara D. Ledsky Jason Pingcheng Li Megan F. Burke Eric Farber-Eger Daniel S. Perrien Ravindra Kumar Kathleen E. Corey Quinn S. Wells Kenneth D. Bloch Charles C. Hong Donald B. Bloch Rajeev Malhotra
author_facet	Timothy E. Thayer Christian L. Lino Cardenas Trejeeve Martyn Christopher J. Nicholson Lisa Traeger Florian Wunderer Charles Slocum Haakon Sigurslid Hannah R. Shakartzi Caitlin O’Rourke Georgia Shelton Mary D. Buswell Hanna Barnes Leif R. Neitzel Clara D. Ledsky Jason Pingcheng Li Megan F. Burke Eric Farber-Eger Daniel S. Perrien Ravindra Kumar Kathleen E. Corey Quinn S. Wells Kenneth D. Bloch Charles C. Hong Donald B. Bloch Rajeev Malhotra
author_sort	Timothy E. Thayer
title	The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
title_short	The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
title_full	The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
title_fullStr	The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
title_full_unstemmed	The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
title_sort	role of bone morphogenetic protein signaling in non-alcoholic fatty liver disease
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0b2d4d623f694b79a8b273377b95590c
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The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease

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