Sodium acetate improves disrupted glucoregulation and hepatic triglyceride content in insulin-resistant female rats: involvement of adenosine deaminase and dipeptidyl peptidase-4 activities
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Combined oral contraceptive (COC) treatment has been shown to be associated with glucose deregulation and increased triglyceride levels, but the mechanisms are elusive. Soluble dipeptidyl peptidase-4 (sDPP-4) and adenosine deaminase (ADA) are involved in the initiation and/or progression of cardiometabolic disorders. We therefore, hypothesized that increased DPP-4 and ADA activities are involved in glucose deregulation and hepatic triglyceride accumulation induced by COC treatment. This study also investigated whether short-chain fatty acid, acetate, would protect against COC-induced dysmetabolic effects. Female Wistar rats received (p.o.) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel) with or without sodium acetate (ACE; 200 mg) for 8 weeks. Treatment with COC led to increased plasma triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, insulin resistance, and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic triglycerides (TG), TG/HDL-cholesterol ratio, malondialdehyde, uric acid, lactate dehydrogenase, DPP-4, ADA, and xanthine oxidase (XO) activities. On the other hand, COC led to reduction in nitric oxide level. However, ACE significantly ameliorated the alterations induced by COC treatment, but XO activity remains elevated during COC treatment. This result also demonstrates that increased DPP-4 and ADA activities are at least in part involved in glucose deregulation and hepatic TG accumulation induced by COC treatment. Therefore, sodium acetate would impact positively on cardiometabolic disorders, at least in part, by inhibition of DPP-4 and ADA activities.
KeywordsAdenosine deaminase Combined oral contraceptive Dipeptidyl peptidase-4 Hepatic insulin resistance
This research was done without specific grant from any funding agencies in the public, commercial or not-for-profit sectors. The authors appreciate the technical support from the HOPE Cardiometabolic Research Team, Ilorin, Nigeria.
Author contribution statement
OLA conceived and designed the research. OTE conducted experiments. OLA contributed new reagents and analytical kits. OTE, MOS and OLA analyzed and interpreted data. OLA, OTE and MOS drafted the manuscript. OTE, MOS, and OLA read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
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