Inhibition of dipeptidyl peptidase-4 averts Free Fatty acids deposition in the hearts of oral estrogen-progestin contraceptive-induced hyperinsulinemic female rats

Free fatty acids deposition in non-adipose tissues such as the heart is a characteristic of insulin resistant states which features 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 free fatty acid (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, Triglyceride/high density lipoprotein (TG/HDL) ratio, adenosine deaminase/xanthine oxidase/uric acid pathway, 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 and TG/HDL-C ratio and alkaline phosphatase. These were accompanied by reduced adenosine deaminase/xanthine oxidase/uric acid (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 disordersThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author