Puerarin Improves Glucose and Lipid Metabolism in Type 2 Diabetes by Regulating Gut Microbiota Homeostasis and Promoting Adipose Tissue Thermogenesis

Type 2 diabetes (T2D) is a chronic disease that seriously threatens human health. Puerarin, the primary bioactive component of Pueraria lobata , alleviates T2D through multiple mechanisms, including protection of pancreatic β-cells, enhancement of insulin sensitivity, and antioxidant effects. However, its specific mechanisms of action against T2D remain incompletely understood. This study aimed to investigate the curative effects of puerarin in ameliorating glucose and lipid metabolism disorders in T2D mice by preserving gut microbiota homeostasis and promoting adipose tissue thermogenesis. To achieve this, 16S rRNA gene sequencing and metabolomics were employed to assess its effects on gut microbiota and fecal metabolites, while qRT-PCR and western blot were conducted to evaluate its impact on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. The results demonstrated that puerarin promoted gut microbiota homeostasis and elevated butyrate levels. Specifically, it increased the abundance of beneficial bacteria (Lactobacillaceae, Muribaculaceae, and Akkermansiaceae) and reduced the abundance of harmful bacteria (Desulfovibrionaceae, Marinifilaceae, and Helicobacteraceae). Moreover, puerarin enhanced brown adipose tissue (BAT) activity via the PI3K/AKT pathway and induced a browning phenotype in white adipose tissue (WAT) through the PPARγ pathway. These effects promoted mitochondrial biosynthesis, lipolysis, glucose utilization, and energy expenditure. Puerarin also increased glucagon-like peptide-1 (GLP-1) secretion, thereby further improving insulin sensitivity. In conclusion, this study confirms that puerarin improves glucose and lipid metabolism disorders in T2D mice by regulating gut microbiota homeostasis and promoting adipose tissue thermogenesis, which holds considerable potential for the treatment of T2D.