Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats
Open accessAbstract
Aims/hypothesis Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM.Materials and methods Rats received high-fat (HFD) or low-fat (LFD) diets for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile function and insulin signalling were assessed in papillary muscles and ventricular lysates, respectively.Results Fasting and post-load blood glucose levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed structural changes and triglyceride accumulation. HFD-muscles developed higher baseline and maximum forces, but showed impaired recovery from higher workloads. Insulin-associated modulation of Ca2+-induced force augmentation was abolished in HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol 3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of phospholamban, a critical regulator of myocardial contractility, was decreased in HFD-hearts (p < 0.05).Conclusions/interpretation HFD induced a hypertrophy-like cardiac phenotype, characterised by a higher basal contractile force, an impaired recovery from increased workloads and decreased insulin-mediated protection against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin resistance and phospholamban hypophosphorylation. Our data suggest that myocardial insulin resistance, resulting from exposure to excessive alimentary fat, may contribute to the pathogenesis of diabetes-related heart disease.
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High-fat feeding that is associated with the development of insulin resistance and obesity is associated with development of LV dysfunction in many but not all studies.
“In contrast, high-fat feeding that is associated with the development of insulin resistance and obesity is associated with development of LV dysfunction in many (269, 273, 296) but not all studies (40).”
From Cardiac remodeling in obesity (2008) · cites this paper as [269]
Seven weeks of high-fat feeding in Wistar rats results in LVH.
“Likewise, high-fat feeding of Sprague-Dawley rats for up to 14 wk has not been associated with LVH despite the development of obesity (40, 299), whereas 7 wk of high-fat feeding in Wistar rats results in LVH (269).”
From Cardiac remodeling in obesity (2008) · cites this paper as [269]
Treatment of Wistar rats with a high-fat diet for 7 wk was associated with LV hypertrophy, triglyceride accumulation, and insulin resistance; papillary muscles revealed an increase in baseline and maximal force generation, but impaired recovery from high work loads, impaired insulin-mediated augmentation of calcium-mediated contractility, and reduced insulin-mediated phosphorylation of phospholamb
“Treatment of Wistar rats with a high-fat diet for 7 wk was associated with LV hypertrophy triglyceride accumulation and insulin resistance. Papillary muscles revealed an increase in baseline and maximal force generation, but impaired recovery from high work loads, impaired insulin-mediated augmentation of calcium-mediated contractility, and reduced insulin-mediated phosphorylation of phospholamban”
From Cardiac remodeling in obesity (2008) · cites this paper as [269]
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References 54 · Cited by 256
- Authors
- Ouwens, D. M., Boer, C., Fodor, M., de Galan, P., Heine, R. J., Maassen, J. A., & Diamant, M.
- Affiliations
- Leiden University Medical Center (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Ouwens, D. M.
- Venue
- Diabetologia
- Published
- 2005-04-30
- Volume
- 48
- Issue
- 6
- Pages
- 1229-1237
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2035050651
- Cited by
- 256
- References
- 54
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 11 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 15 · 2019: 8 · 2018: 12 · 2017: 11 · 2016: 7 · 2015: 20 · 2014: 19 · 2013: 20 · 2012: 9
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Vrije Universiteit Amsterdam
- Leids Universitair Medisch Centrum
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- diabetic cardiomyopathy, myocardial insulin resistance, high-fat diet, cardiac hypertrophy, cardiac contractility, phospholamban phosphorylation, insulin signaling, IRS-1, PI3K/Akt signaling, glycogen synthase kinase-3β, endothelial nitric oxide synthase, forkhead transcription factor, calcium overload, triglyceride accumulation, type 2 diabetes, cardiac dysfunction
- MeSH terms
- Animals, Dietary Fats, Heart, Heart Ventricles, Insulin, Male, Myocardial Contraction, Papillary Muscles, Triglycerides, Signal Transduction, Rats, Wistar, Diet, Fat-Restricted, Models, Animal, Rats
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