The ameliorating effect of intermittent fasting on intestinal glucagon-like peptide 1 in rats fed a high-fat diet via the Farnesoid X receptor and the Melanocortin-4 receptor

Obesity and its associated intestinal inflammatory responses represent a significant global challenge. (IF) is a dietary intervention demonstrating various health benefits, including weight loss, enhanced metabolic health, and increased longevity. However, its effect on the intestinal inflammation induced by high-fat diet (HFD) is still not fully comprehended. Thirty-four male Sprague-Dawley rats were randomized into three groups: Control (fed standard chow diet for 24 weeks); the HFD group (fed HFD for 24 weeks); and the HFD + IF group (fed HFD for 12 weeks, followed by an alternate day regimen of fasting and HFD for 12 weeks). The results revealed that IF significantly reduced body weight, food intake, and blood glucose levels compared to the HFD group. Furthermore, rats undergoing the intermittent fasting regimen exhibited a significant reduction in resting time, along with increased durations of grooming and exploration when compared to those on HFD. IF significantly reduced HFD-induced intestinal oxidative stress by lowering malondialdehyde levels and substantially increasing intestinal total antioxidant capacity, consistent with histopathological findings of gastric and intestinal tissues. The investigation of the underlying mechanisms revealed that IF significantly increased the intestinal expression of Farnesoid X receptor (FXR), glucagon-like peptide 1 (GLP-1), and melanocortin-4 receptors (MC4R), with a significant decrease in gastrointestinal peroxisome proliferator-activated receptor-γ (PPAR-γ) compared to the HFD group. The findings indicate that IF can mitigate HFD-induced intestinal inflammation via the FXR/GLP-1/MC4R/ PPAR-γ pathway. This highlights the need for further research to elucidate these mechanisms.