Dipeptidyl peptidase‐4 inhibitors and aerobic exercise synergistically protect against liver injury in ovariectomized rats

: Menopause increases the risk of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of incretin and/ or exercise on the hepatic fat accumulation in ovariectomized rats. Rats were divided into five groups: Group 1: Control rats, Group 2: Ovariectomized rats, Group 3: Ovariectomized rats + Dipeptidyl peptidase-4 inhibitor (DPPi) (30 mg/kg/day, orally), Group 4: Ovariectomized rats + swimming, and Group 5: Ovariectomized rats + swimming + DPPi. After 6 weeks, Alanine aminotransferase (ALT), glucose, insulin, HOMA IR (Homeostatic Model Assessment for Insulin Resistance), FFA (free fatty acids), Tumor necrosis factor alpha (TNF α), IL6, IL1B levels were measured in blood. The livers were collected for Hematoxylin and eosin (H&E) examination and evaluation of hepatic gene expression of SREBP (sterol regulatory element-binding protein1c), PPAR α (peroxisome proliferator-activated receptor alpha), ACC 1 (acetyl-CoA carboxylase), LC3 (microtubule-associated protein 1 light chain 3), SIRT (sirtuin), hepatic triglycerides, IL6, IL10, caspase 3 and AMPK (adenosine monophosphate-activated protein kinase). A significant increase in ALT level and area of liver tissue defects with a significant increase in glucose HOMA IR, serum FFA, IL6, IL1B, TNF α, liver TGs (triglycerides), inflammation, apoptosis, SREBP1c, ACC1 were found in ovariectomized rats as compared to control group with a significant decrease in PPAR α, LC3, AMPK and SIRT1. DPPi treated rats with and without exercise showed a significant improvement in ALT and area of liver tissue defects, inflammation and apoptosis and serum IL6, IL1B, TNF α, FFA, liver LC3, SIRT1, AMPK, TGs, PPAR α, ACC1 and SREBP1c as compared to the ovariectomized group. Findings from the study confirm the derangement of fat metabolism in the ovariectomized rats and showed that incretin-based therapy and exercise synergistically improved liver fat metabolism, achieved significant beneficial metabolic effects and offer full protection against NAFLD.