Metabolic benefits of 1,3-diacylglycerol in type 2 diabetes mellitus and its association with gut microbiota-derived SCFAs-GPR41-GLP-1 signaling

1,3-Diacylglycerol (1,3-DAG) is a dietary lipid with known lipid-lowering effects, yet its role in type 2 diabetes mellitus (T2DM) and gut microbiota regulation remains unclear. This study investigated the effects of 1,3-DAG on glucose-lipid metabolism and gut microbiota- short chain fatty acid (SCFA)-G protein-coupled receptors (GPR41) signaling in T2DM rats. Male Wistar rats were fed a high-fat, high-sugar diet with weekly Streptozotocin (STZ) injections (30 mg kg^-1) for 4 weeks to induce T2DM. After confirming stable hyperglycemia, rats were randomly divided into four groups: healthy control, T2DM model, low-dose 1,3-DAG (50% DAG + 50% TAG), and high-dose 1,3-DAG (100% DAG). Interventions lasted 8 weeks. Compared to the T2DM model group, both low- and high-dose DAG significantly reduced fasting blood glucose, insulin, and triglycerides, with levels approaching those in the control group. 1,3-DAG also restored colonic morphology, elevated GPR41 expression, and increased Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion, while reducing serum lipopolysaccharide (LPS). Microbiota analysis showed enrichment of <i>Bacteroidota</i> and depletion of <i>Proteobacteria</i>, with increased SCFA levels including acetate, propionate, and valerate. Importantly, <i>Bacteroidota</i>-related taxa were negatively correlated with glycemic and lipid markers, while <i>Proteobacteria</i> taxa showed positive correlations with low-density lipoprotein cholesterol (LDL-C) and negative correlations with high-density lipoprotein cholesterol (HDL-C). 1,3-DAG significantly improved glycemic control, lipid metabolism and intestinal barrier integrity in T2DM rats. These benefits may be mediated through the gut microbiota-SCFA-GPR41-GLP-1 signaling axis. The findings suggest that 1,3-DAG is a promising dietary intervention for T2DM. Further clinical studies are warranted to validate its long-term efficacy and therapeutic potential.