Abstract

Objective: GLP-1 is a key incretin hormone that not only regulates glucose metabolism but also contributes to energy expenditure and adipose tissue remodeling. However, the integrative role of GLP-1 in coordinating lipid oxidation and thermogenic gene expression in adipose tissues remains incompletely understood. Thus, we investigated anti-obesity effects of NEXITOP including regulation of incretin hormones and thermogenic genes related to fat metabolism. Materials and Methods: Male C57BL/6J mice were fed a 45% high-fat diet (HFD) for 14 weeks to induce obesity, followed by oral administration of NEXITOP, a novel GLP-1 regulator for 12 weeks. Serum incretin hormones markers (GLP-1, GLP-2, DPP-4) and glucose levels were analyzed, and expression of genes encoding thermogenic and fat oxidation markers (UCP1, PGC1α, ACOX1) was examined in white and brown adipose tissue. Results: NEXITOP administration significantly increased circulating GLP-1 and GLP-2 levels while reducing DPP-4 activity and fasting glucose. These hormonal changes were accompanied by a significant reduction in final body weight and visceral fat mass compared with the HFD group. At the tissue level, both white and brown adipose tissue exhibited upregulated expression of UCP1, PGC1α, and ACOX1, suggesting enhanced mitochondrial and peroxisomal fatty acid oxidation. Conclusion: NEXITOP ameliorates HFD-induced obesity by enhancing GLP-1-mediated signaling and reprogramming adipose tissue metabolism toward an oxidative and thermogenic phenotype. These findings highlight a potential therapeutic strategy combining incretin modulation and adipose metabolic remodeling for obesity and metabolic disorders.

Graphical Abstract