Scientific Reports (Jun 2020)
The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease
- 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
Affiliations
- Timothy E. Thayer
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Christian L. Lino Cardenas
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Trejeeve Martyn
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Christopher J. Nicholson
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Lisa Traeger
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Florian Wunderer
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Charles Slocum
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Haakon Sigurslid
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Hannah R. Shakartzi
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Caitlin O’Rourke
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Georgia Shelton
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Mary D. Buswell
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Hanna Barnes
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Leif R. Neitzel
- Department of Medicine, University of Maryland School of Medicine
- Clara D. Ledsky
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Jason Pingcheng Li
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Megan F. Burke
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Eric Farber-Eger
- Department of Medicine, Vanderbilt University Medical Center
- Daniel S. Perrien
- Department of Medicine, Vanderbilt University Medical Center
- Ravindra Kumar
- Acceleron Pharma, Inc.
- Kathleen E. Corey
- GI Unit, Massachusetts General Hospital, Harvard Medical School
- Quinn S. Wells
- Department of Medicine, Vanderbilt University Medical Center
- Kenneth D. Bloch
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- Charles C. Hong
- Department of Medicine, University of Maryland School of Medicine
- Donald B. Bloch
- Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School
- Rajeev Malhotra
- Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School
- DOI
- https://doi.org/10.1038/s41598-020-66770-8
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 13
Abstract
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.
