Thyroid Hormone Reverses Aging-Induced Myocardial Fatty Acid Oxidation Defects and Improves the Response to Acutely Increased AfterloadReport as inadecuate




Thyroid Hormone Reverses Aging-Induced Myocardial Fatty Acid Oxidation Defects and Improves the Response to Acutely Increased Afterload - Download this document for free, or read online. Document in PDF available to download.

Background

Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to the development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase PDH to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone supplementation reverses these defects.

Methods

Studies were performed on young Young, 4–6 months and aged Old, 22–24 months C57-BL6 mice at standard 50 mmHg and high afterload 80 mmHg. Another aged group received thyroid hormone for 3 weeks Old-TH, high afterload only. Function was measured in isolated working hearts along with substrate fractional contributions Fc to the citric acid cycle CAC using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin.

Results

Old mice maintained cardiac function under standard workload conditions, despite a marked decrease in unlabeled presumably palmitate Fc and relatively similar individual carbohydrate contributions. However, old mice exhibited reduced palmitate oxidation with diastolic dysfunction exemplified by lower -dP-dT. Thyroid hormone abrogated the functional and substrate flux abnormalities in aged mice.

Conclusion

The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.



Author: Dolena Ledee, Michael A. Portman, Masaki Kajimoto, Nancy Isern, Aaron K. Olson

Source: http://plos.srce.hr/



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