The synergistic ameliorative activity of peroxisome proliferator‐activated receptor‐alpha and gamma agonists, fenofibrate and pioglitazone, on hippocampal neurodegeneration in a rat model of insulin resistance

Insulin resistance (IR) is a risk factor for metabolic disorders and neurodegeneration. Peroxisome proliferator-activated receptor (PPAR) agonists have been proven to mitigate the neuronal pathology associated with IR. However, synergetic efficacy of these yet be fully described. Hence, we aimed investigate PPARα/γ (fenofibrate pioglitazone) on high-fat diet (HFD) streptozotocin (STZ)-induced hippocampal Male Wistar rats (200 ± 25 mg/body weight [BW]) were divided into five groups. The experimental groups fed an HFD 12 weeks coupled 5 days STZ injection (30 mg/kg/BW, i.p) induce Fenofibrate (FEN; 100 orally), pioglitazone (PIO; 20 their combination administered 2 postinduction. Behavioral tests conducted, blood was collected determine insulin sensitivity after treatment. Animals killed assessment oxidative stress, cellular morphology characterization, astrocytic evaluation. HFD/STZ-induced IR increased malondialdehyde (MDA) levels decreased glutathione (GSH) levels. Evidence alterations overexpression protein observed in hippocampus. By contrast, monotherapy FEN PIO GSH level (p < 0.05), MDA improved expression. Furthermore, combined treatment led therapeutic activities compared monotherapies. In conclusion, exerted synergistic effect