Nuciferine ameliorates high-fat diet-induced disorders of glucose and lipid metabolism in obese mice based on the gut-liver axis

High-fat diets (HFDs) can trigger lipid accumulation, insulin resistance, and inflammatory responses in the body, causing glucose and lipid metabolism dysfunction. This study aimed to explore the role of nuciferine on HFD-induced disorders of glucose and lipid metabolism in obesity mice models, and further to identify the possible underlying mechanisms. In our experiments, nuciferine effectively ameliorated HFD-induced insulin resistance by IRS/PI3K/AKT pathway, and alleviated HFD-induced lipid accumulation via AMPK-mediated regulation of FAS and ATGL expression. Nuciferine also suppressed HFD-induced intestinal pathological damage, as evidenced by the improvement of intestinal barrier integrity and the increasing in expressions of tight junction proteins of claudin, ZO-1, and occludin. In addition, 16S rRNA gene sequencing of the fecal microbiota suggested that nuciferine changed the diversity and the composition of gut microbiota in HFD-fed mice. Nuciferine decreased the ratio of Firmicutes/Bacteroidetes, the relative abundance of LPS-producing genus Desulfovibrio and the bacteria which involved in lipid metabolism. In summary, nuciferine ameliorated the disorders of glucose and lipid metabolism in obese mice via balancing the gut-liver axis.