Effects of diet-induced obesity and bariatric surgery (sleeve gastrectomy) on gene expression and signaling pathways in mouse salivary glands

Obesity is increasingly recognized to affect oral and salivary gland health, yet the transcriptomic alterations underlying obesity-related salivary gland dysfunction and the effects of bariatric surgery remain incompletely understood. In this study, we investigated the impact of obesity and bariatric surgery on salivary gland structure and function at the transcriptomic level using a diet-induced obesity (DIO) mouse model and a sleeve gastrectomy (SG) model. Histological changes were evaluated by hematoxylin and eosin (H&E) staining, and transcriptome sequencing was performed to identify differentially expressed genes (DEGs) among control, obese, and surgery groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify key biological pathways, followed by protein–protein interaction (PPI) network analysis and transcription factor regulatory network prediction. Histological analysis revealed acinar cell swelling and ductal dilation in salivary glands of obese mice. Transcriptomic profiling showed significant enrichment of DEGs in inflammation- and immune-related pathways, including the T cell receptor signaling pathway. Compared with the obese group, bariatric surgery partially improved structural alterations and was associated with downregulation of immune-related genes (Cd19 and Cd3e) and upregulation of lipid metabolism- and macrophage-related genes (Fabp4 and Adgre1). Transcription factor analysis suggested that Tcf7 and Irf4 may be involved in obesity-related salivary gland dysfunction through regulation of inflammation-related genes, and that transcriptional regulatory networks were remodeled after bariatric surgery. These findings indicate that obesity is closely associated with enhanced inflammatory and immune responses and dysregulation of metabolism-related pathways in salivary glands, while bariatric surgery may partially improve molecular features related to salivary gland structure and function by remodeling inflammation-immune and lipid metabolism-related pathways.