Oral ethinylestradiol-levonorgestrel attenuates cardiac glycogen and triglyceride accumulation in high fructose female rats by suppressing pyruvate dehydrogenase kinase-4.

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.