Inhibition of dipeptidyl peptidase-4 averts Free Fatty acids deposition in the hearts of oral estrogen-progestin contraceptive-induced hyperinsulinemic female rats.
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Date
2021
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Publisher
Canadian Science Publishing.
Abstract
Free fatty acid (FFA) deposition in non-adipose tissues such as the heart is a characteristic of insulin resistant states which feature hyperinsulinemia and dipeptidyl peptidase-4 (DPP-4) activation. Estrogen–progestin oral contraceptives (OC) treatment reportedly increased DPP-4 activity in rat tissue, and DPP-4 inhibitors have anti-diabetic and anti-inflammatory properties. This study aims to investigate the effects of DPP-4 inhibition on cardiac FFA deposition in estrogen–progestin-treated female rats. From our data, estrogen–progestin OC exposure in female rats led to elevated plasma insulin, cardiac DPP-4 activity, FFA and triglyceride (TG) accumulation, TG/high-density lipoprotein cholesterol (TG/HDL-C) ratio, adenosine deaminase/xanthine oxidase/uric acid pathway (ADA/XO/UA), lipid peroxidation, glycogen synthase activity, and alanine phosphatase; whereas cardiac glucose-6-phosphate dehydrogenase, Na+/K+-ATPase and nitric oxide (NO) were decreased. However, DPP-4 inhibition resulted in decreased plasma insulin, cardiac DPP-4 activity, FFA, TG, TG/HDL-C ratio, and alkaline phosphatase. These were accompanied by reduced ADA/XO/UA pathway, lipid peroxidation, and augmented NO and Na+/K+-ATPase in estrogen–progestin OC-treated rats. DPP-4 inhibition attenuated cardiac lipid deposition accompanied by reduced activity in the ADA/XO/UA pathway in estrogen–progestin OC-treated female rats. DPP-4 is therefore a plausible therapeutic target in cardiometabolic disorders.
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Keywords
Cardiac lilid accumulation, Cardiac metabolic disorders, Dipeptidyl peptidase-4, Hormonal contraceptive, Hyperinsulinemia
Citation
Adegoke, T.E., Sabinari, I.W., Areola, E.D., Ajao, F.O., Asafa, O.O., Soluoku, T.K., Bello, A., Adesanmi, A.M., Yusuf, S.O., Omoleye, A.O., Ayinla, M.T. & Olatunji, L.A. (2021). Inhibition of dipeptidyl peptidase-4 averts Free Fatty acids deposition in the hearts of oral estrogen-progestin contraceptive-induced hyperinsulinemic female rats. Canadian Journal of Physiology and Pharmacology. 99(12); 1216-1323, Published by Canadian Science Publishing. Available online at https://cdnsciencepub.com/toc/cjpp/99/12