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

Animals Biomarkers / blood Bone Morphogenetic Proteins / metabolism Cell Line, Tumor Diacylglycerol O-Acyltransferase / metabolism Gene Expression Regulation / drug effects Lipid Metabolism / drug effects Mice Non-alcoholic Fatty Liver Disease / blood Pyrazoles / pharmacology Pyrimidines / pharmacology Signal Transduction / drug effects Smad Proteins / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
19 06 2020
Historique:
received: 13 03 2019
accepted: 05 05 2020
entrez: 21 6 2020
pubmed: 21 6 2020
medline: 15 12 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-020-66770-8 PMID: 32561790 PMC: PMC7305229
pubmed: 32561790
doi: 10.1038/s41598-020-66770-8
pii: 10.1038/s41598-020-66770-8
pmc: PMC7305229
doi:

Substances chimiques

Biomarkers 0
Bone Morphogenetic Proteins 0
LDN 193189 0
Pyrazoles 0
Pyrimidines 0
Smad Proteins 0
DGAT2 protein, mouse EC 2.3.1.20
Diacylglycerol O-Acyltransferase EC 2.3.1.20

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9831

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : R01HL142809
Pays : International
Organisme : NIAMS NIH HHS
ID : T32 AR007592
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL111210
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : K08HL111210
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL142809
Pays : United States

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Auteurs

Timothy E Thayer (TE)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.

Christian L Lino Cardenas (CL)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
ORCID: 0000-0001-5491-4375

Trejeeve Martyn (T)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Christopher J Nicholson (CJ)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Lisa Traeger (L)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Florian Wunderer (F)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
ORCID: 0000-0003-1559-0800

Charles Slocum (C)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Haakon Sigurslid (H)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Hannah R Shakartzi (HR)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Caitlin O'Rourke (C)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Georgia Shelton (G)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Mary D Buswell (MD)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Hanna Barnes (H)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Leif R Neitzel (LR)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.

Clara D Ledsky (CD)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Jason Pingcheng Li (JP)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Megan F Burke (MF)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Eric Farber-Eger (E)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.

Daniel S Perrien (DS)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.

Ravindra Kumar (R)

Acceleron Pharma, Inc., Cambridge, MA, United States.

Kathleen E Corey (KE)

GI Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Quinn S Wells (QS)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.

Kenneth D Bloch (KD)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Charles C Hong (CC)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
ORCID: 0000-0002-0424-8252

Donald B Bloch (DB)

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Center for Immunology and Inflammatory Diseases and the Division of Rheumatology, Allergy, and Immunology of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Rajeev Malhotra (R)

Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. rmalhotra@mgh.harvard.edu.
ORCID: 0000-0003-0120-4630

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Protéines morphogénétiques osseuses › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Acyltransferases › Diacylglycerol O-acyltransferase › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Pyrazoles › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › The Role of Bone Morphogenetic Protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines Smad › The Role of Bone Morphogenetic Protein...