Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure
Tsunehisa Yamamoto, … , E. Douglas Lewandowski, Daniel P. Kelly
Tsunehisa Yamamoto, … , E. Douglas Lewandowski, Daniel P. Kelly
Published March 16, 2023
Citation Information: J Clin Invest. 2023. https://doi.org/10.1172/JCI162309.
View: Text | PDF
Research In-Press Preview Cardiology

RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure

  • Text
  • PDF
Abstract

During development of heart failure, capacity for cardiomyocyte fatty acid oxidation (FAO) and ATP production is progressively diminished contributing to pathologic cardiac hypertrophy and contractile dysfunction. Receptor interacting protein 140 (RIP140; Nrip1) has been shown to function as a transcriptional co-repressor of oxidative metabolism. We found that mice with striated muscle deficiency of RIP140 (strNrip1-/-) exhibit increased expression of a broad array of genes involved in mitochondrial energy metabolism and contractile function in heart and skeletal muscle. strNrip1-/- mice were resistant to the development of pressure overload-induced cardiac hypertrophy, and cardiomyocyte-specific RIP140 deficient (csNrip1-/-) mice were defended against development of heart failure caused by pressure overload combined with myocardial infarction. Genomic enhancers activated by RIP140 deficiency in cardiomyocytes were enriched in binding motifs for transcriptional regulators of mitochondrial function (estrogen-related receptor) and cardiac contractile proteins (myocyte enhancer factor 2). Consistent with a role in the control of cardiac fatty acid oxidation, loss of RIP140 in heart resulted in augmented triacylglyceride turnover and FA utilization. We conclude that RIP140 functions as a suppressor of a transcriptional regulatory network that controls cardiac fuel metabolism and contractile function, representing a potential therapeutic target for heart failure.

Authors

Tsunehisa Yamamoto, Santosh K. Maurya, Elizabeth Pruzinsky, Kirill Batmanov, Yang Xiao, Sarah M. Sulon, Tomoya Sakamoto, Yang Wang, Ling Lai, Kendra S. McDaid, Swapnil V. Shewale, Teresa C. Leone, Timothy R. Koves, Deborah M. Muoio, Pieterjan Dierickx, Mitchell A. Lazar, E. Douglas Lewandowski, Daniel P. Kelly

×

Full Text PDF | Download (4.01 MB)


Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts