Adiponectin-mediated modulation of hypertrophic signals in the heart
Open accessAbstract
Patients with diabetes and other obesity-linked conditions have increased susceptibility to cardiovascular disorders. The adipocytokine adiponectin is decreased in patients with obesity-linked diseases. Here, we found that pressure overload in adiponectin-deficient mice resulted in enhanced concentric cardiac hypertrophy and increased mortality that was associated with increased extracellular signal-regulated kinase (ERK) and diminished AMP-activated protein kinase (AMPK) signaling in the myocardium. Adenovirus-mediated supplemention of adiponectin attenuated cardiac hypertrophy in response to pressure overload in adiponectin-deficient, wild-type and diabetic db/db mice. In cultures of cardiac myocytes, adiponectin activated AMPK and inhibited agonist-stimulated hypertrophy and ERK activation. Transduction with a dominant-negative form of AMPK reversed these effects, suggesting that adiponectin inhibits hypertrophic signaling in the myocardium through activation of AMPK signaling. Adiponectin may have utility for the treatment of hypertrophic cardiomyopathy associated with diabetes and other obesity-related diseases.
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There is an inverse relationship between adiponectin and leptin levels, with low adiponectin levels indicating metabolic and cardiovascular disease.
“There is an inverse relationship between adiponectin and leptin levels, with low adiponectin levels indicating metabolic and cardiovascular disease [36].”
From Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population (2016) · cites this paper as [36]
Adiponectin has antidiabetic effects and antagonizes the progression of DCM by exhibiting potent anti-hypertrophic activity in cardiomyocytes and diminishing cardiac cell death by inhibiting inflammation.
“Adiponectin has antidiabetic effects and antagonizes the progression of DCM by exhibiting potent anti-hypertrophic activity in cardiomyocytes and diminishing cardiac cell death by inhibiting inflammation [36-38].”
From Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population (2016) · cites this paper as [36]
Pressure overload-induced concentric hypertrophy was enhanced in adiponectin-deficient mice and led to increased mortality that was corrected by adiponectin replacement.
“Similarly, pressure overload-induced concentric hypertrophy was enhanced in adiponectin-deficient mice and led to increased mortality that was corrected by adiponectin replacement (320).”
From Cardiac remodeling in obesity (2008) · cites this paper as [320]
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- Authors
- Shibata, R., Ouchi, N., Ito, M., Kihara, S., Shiojima, I., Pimentel, D. R., Kumada, M., Sato, K., Schiekofer, S., Ohashi, K., Funahashi, T., Colucci, W. S., & Walsh, K.
- Affiliations
- Boston University (US)
- The University of Osaka (JP)
- Corresponding author
- Walsh, Kenneth
- ORCID
- Venue
- Nature Medicine
- Published
- 2004-11-21
- Volume
- 10
- Issue
- 12
- Pages
- 1384-1389
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC2828675
- OpenAlex
- W2130006068
- Cited by
- 671
- References
- 25
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 9 · 2023: 19 · 2022: 19 · 2021: 18 · 2020: 19 · 2019: 26 · 2018: 23 · 2017: 17 · 2016: 36 · 2015: 25 · 2014: 39 · 2013: 42 · 2012: 45
- FWCI
- 24.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Uehara Memorial Foundation
- National Institutes of Health
- Japan Society for the Promotion of Science
- National Institute on Aging (R01AG015052, AG17241, R37AG015052, AG15052, R01AG017241)
- National Heart, Lung, and Blood Institute (HL20612, R01HL061639, HL-66957, T32HL007224, P01HL066957, HL 61639)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-40197, R01AR040197)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- adiponectin, cardiac hypertrophy, pressure overload, AMPK, ERK signaling, db/db mice, diabetic cardiomyopathy, hypertrophic cardiomyopathy, obesity, myocardium, cardiomyocytes, adenoviral gene transfer
- MeSH terms
- Adenoviridae, Animals, Blood Pressure, Echocardiography, Cardiomegaly, Heart Rate, Immunohistochemistry, Mice, Inbred C57BL, Multienzyme Complexes, Myocardium, Obesity, Blotting, Western, Signal Transduction, Protein Serine-Threonine Kinases, Gene Transfer Techniques, Mice, Knockout, Myocytes, Cardiac, Intercellular Signaling Peptides and Proteins, Extracellular Signal-Regulated MAP Kinases, Mice, Adiponectin, AMP-Activated Protein Kinases
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