Key result
Transverse aortic constriction induced progressive cardiac hypertrophy and dysfunction in non-diabetic mice, but affected cardiac function only mildly in diabetic mice.
Why the study?
Does diabetes-induced metabolic adaptation prevent heart failure development upon pressure overload in mice?
Does diabetes-induced metabolic adaptation prevent heart failure development upon pressure overload in mice?
Cardiac metabolic adaptations in diabetic mice appear to protect against pressure overload-induced heart failure, suggesting that balancing glucose and fatty acid utilization may be beneficial.
Should not inform clinical care; hypothesis-generating for attenuated pressure-overload response in diabetes.
AIMS: Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. METHODS AND RESULTS: Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. CONCLUSION: The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function.
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Abdurrachim et al. (2017) studied Heart failure. Transverse aortic constriction (TAC) vs. Non-diabetic mice was evaluated on Cardiac hypertrophy and dysfunction. Transverse aortic constriction induced progressive cardiac hypertrophy and dysfunction in non-diabetic mice, but affected cardiac function only mildly in diabetic mice.
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