Oral ethinylestradiol-levonorgestrel attenuates cardiac glycogen and triglyceride accumulation in high fructose female rats by suppressing pyruvate dehydrogenase kinase-4
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Fructose (FRU) intake has increased dramatically in recent decades with a corresponding increased incidence of insulin resistance (IR), particularly in young adults. The use of oral ethinylestradiol-levonorgestrel (EEL) formulation is also common among young women worldwide. The present study aimed at determining the effect of EEL on high fructose-induced cardiac triglyceride (TG) and glycogen accumulation. The study also investigated the possible involvement of pyruvate dehydrogenase kinase-4 (PDK-4) in EEL and/or high fructose metabolic effects on the heart. Ten-week-old female Wistar rats were allotted into four groups. The control, EEL, FRU, and EEL + FRU rats received distilled water (vehicle, p.o.), 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel (p.o.), 10% fructose (w/v), and 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel and 10% fructose, respectively, daily for 8 weeks. Data showed that EEL or high fructose caused IR‚ impaired glucose tolerance‚ hyperlipidemia‚ increased plasma lactate, lactate dehydrogenase, PDK-4, uric acid, xanthine oxidase (XO), adenosine deaminase (ADA), malondialdehyde (MDA), cardiac uric acid, TG, TG/HDL- cholesterol, glycogen synthesis, MDA, and visceral fat content and reduced glutathione. High fructose also resulted in impaired pancreatic β-cell function, hyperglycemia, and increased cardiac PDK-4, lactate synthesis, and mass. Nonetheless, these alterations were ameliorated in EEL plus high fructose rats. This study demonstrates that high fructose-induced myocardial TG and glycogen accumulation is attributable to increased PDK-4. Besides, EEL could be a useful pharmacological utility for protection against cardiac dysmetabolism by inhibiting PDK-4.
KeywordsCardiac dysfunction Glycogen synthesis Insulin resistance Lipid accumulation PDK-4 Metabolic syndrome
The authors appreciate the technical support from the HOPE Cardiometabolic Research Team, Ilorin, Nigeria.
KSO and LAO conceived and designed the research. KSO conducted the experiments. LAO contributed to the new reagents and analytical kits. KSO and LAO analyzed and interpreted the data. KSO drafted the manuscript. KSO and LAO read and approved the final manuscript.
Compliance with ethical standards
The investigation was conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and was approved by the Institutional Ethical Review Board of University of Ilorin, and every effort was made to minimize both the number of animals used and their suffering.
Conflict of interest
The authors declare that they have no conflicts of interest.
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