Cardiac Lipid Accumulation Associated with Diastolic Dysfunction in Obese Mice
Abstract
Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and β-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 ± 0.4 vs. 2.3 ± 0.4 μg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 ± 0.1 in ob/ob mice and 2.5 ± 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.
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A commonly described feature of most animal models of obesity is increased accumulation of intramyocellular triglycerides in the heart.
“A commonly described feature of most animal models of obesity is increased accumulation of intramyocellular triglycerides in the heart. This has been reported in the hearts of genetic models such as ob/ob and db/db mice (29, 31, 34, 53), Zucker or fa/fa rats (394), and following high-fat feeding (346).”
From Cardiac remodeling in obesity (2008) · cites this paper as [53]
Fewer studies reveal changes in diastolic function in animal models of obesity.
“Fewer studies reveal changes in diastolic function (53, 313).”
From Cardiac remodeling in obesity (2008) · cites this paper as [53]
In animal models of obesity, most in vivo studies reveal mildly impaired systolic function that is absent in younger animals (<12 wk of age) but becomes evident between 12 and 20 wk of age.
“Generally, most studies reveal evidence of mildly impaired systolic function in vivo that is absent in younger animals (<12 wk of age) but become evident between 12 and 20 wk of age (34, 53, 313, 357, 361, 388).”
From Cardiac remodeling in obesity (2008) · cites this paper as [53]
In 10- to 11-wk-old female ob/ob mice, there are minimal changes in LV systolic function under baseline conditions but a reduction in the inotropic response to dobutamine, and evidence of diastolic dysfunction manifested by reduced E/A ratios.
“In 10- to 11-wk-old female ob/ob mice, Christoffersen et al. (53) reported minimal changes in LV systolic function under baseline conditions but a reduction in the inotropic response to dobutamine. They reported evidence of diastolic dysfunction manifested by reduced E/A ratios (53).”
From Cardiac remodeling in obesity (2008) · cites this paper as [53]
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References 39 · Cited by 375
- Authors
- Christoffersen, C., Bollano, E., Lindegaard, M. L. S., Bartels, E. D., Goetze, J. P., Andersen, C. B., & Nielsen, L. B.
- Affiliations
- University of Copenhagen (DK)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Nielsen, Lars B.
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-08-01
- Volume
- 144
- Issue
- 8
- Pages
- 3483-3490
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2113362144
- Cited by
- 375
- References
- 39
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 5 · 2023: 9 · 2022: 16 · 2021: 26 · 2020: 14 · 2019: 8 · 2018: 22 · 2017: 15 · 2016: 17 · 2015: 23 · 2014: 20 · 2013: 22 · 2012: 20
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Hjerteforeningen
- Novo Nordisk
- Novo Nordisk Fonden
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- myocardial lipid accumulation, diastolic dysfunction, obesity, ob/ob mice, leptin deficiency, triglyceride storage, lipid droplets, fatty acid uptake, fatty acid beta-oxidation, cardiomyocytes, systolic function, brain natriuretic peptide
- MeSH terms
- Animals, Apolipoproteins B, Carrier Proteins, Collagen, Diastole, Echocardiography, Fatty Acids, Lipoprotein Lipase, Membrane Proteins, Mice, Obese, Microscopy, Electron, Mitochondria, Heart, Myocardium, Obesity, Oxidation-Reduction, Phosphatidylcholines, Phosphatidylinositols, RNA, Messenger, Systole, Triglycerides, Gene Expression, Mice, Knockout, Natriuretic Peptide, Brain, Leptin, Membrane Transport Proteins, Lipid Metabolism, Fatty Acid Transport Proteins, Mice
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