Ameliorative Effect of Glycerol Monolaurate on Glucose Dyshomeostasis in db/db Mice Associated With the PGC-1α Signaling Pathway and Intestinal Microbiota

Abstract

Glycerol monolaurate (GML) has previously been demonstrated to improve insulin resistance in mice fed a high-fat diet (HFD), yet whether GML can enhance glucose homeostasis in diabetic mice remains uncertain. In the current study, BKS mice and BKS-db/db mice were fed a normal chow diet and administered GML solution by gavage for 9 weeks. Weekly postprandial blood glucose, water intake, and weight were recorded at regular intervals. Serum metabolic indicators, liver gene expression, and intestinal microbiota were also assessed. The results revealed that GML significantly decreased the postprandial blood glucose in the later stage of the feeding period, markedly reduced water intake in db/db mice, maintained body weight, and significantly improved glucose and insulin tolerance. Moreover, GML significantly reduced fasting blood glucose and insulin resistance index. GML also significantly inhibited the proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway, thereby suppressing the gluconeogenic pathway, but activated the gene expression of glucokinase in the glycolysis pathway. GML also significantly altered the gut microbiota, decreasing the abundance of Firmicutes, Lactobacillus, and Lachnospiraceae, while increasing the abundance of Bacteroidetes, Helicobacter, Parabacteroides, and S24-7. Our findings suggest that GML modulates gut microbiota and inhibits the PGC-1α signaling pathway, which may be associated with the improved glucose homeostasis observed.