Abstract
This study aimed to investigate the differential expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in relation to the Toll-like receptor (TLR)/nuclear factor κB (NF-κB) signaling pathway in an obese rat model. A total of 200 8-week-old male Wistar rats were randomly assigned to a control group (Ctrl, n = 40) and an observation group (Obs, n = 160), with obesity induced through a high-fat diet. Following modeling, the Obs group was further divided into a model group, a PI3K/AKT inhibition group, a TLR/NF-κB inhibition group, and a combined PI3K/AKT + TLR/NF-κB inhibition group, with 40 rats in each. Metabolic changes were assessed by monitoring the glucose infusion rate (GIR), as well as conducting an intraperitoneal glucose tolerance test (IPGTT) and an intraperitoneal insulin tolerance test (IPITT). Hematoxylin and eosin staining was utilized to observe morphological changes in adipose tissue, while Western blotting was employed to detect the expression levels of proteins associated with the PI3K/AKT and TLR/NF-κB signaling pathways in adipose tissue. The results indicated that the Obs group exhibited significantly higher blood glucose and insulin levels during the IPGTT and IPITT experiments compared to the Ctrl group (P < 0.05). Additionally, the GIR, as well as the expression levels of p-PI3K and p-AKT proteins in the Obs group, were significantly lower than those in the Ctrl group (P < 0.05). In both the PI3K/AKT inhibition group and the combined PI3K/AKT + TLR/NF-κB inhibition group, the expression of relevant proteins further declined (P < 0.05). These findings suggest that while a high-fat diet decreases the activity of the PI3K/AKT signaling pathway, it concurrently promotes inflammatory responses by upregulating the TLR-4 and NF-κB signaling pathways, indicating a critical role for these pathways in obesity-related metabolic abnormalities.