Modulation Of High-fat-induced Disorders Of Hepatic Glucolipid Metabolism By Nardosinane

The liver plays a vital role in the lipid metabolism of livestock and poultry organisms.When the liver lipid metabolism is disturbed,fatty liver is often induced,which seriously affects the production performance of livestock and poultry and limits the development of livestock industry.With the scale and intensive development of the farming industry,the incidence of fatty liver in livestock and poultry has been increasing,and the prevention and treatment of fatty liver has become a pressing problem in the livestock industry.As one of the common extracts of Nardodendron pine,Nardosinane plays an important role in sedation,promoting nerve growth and protecting myocardium.However,the regulatory effects of Nardosinane on lipid metabolism and intestinal microflora have not been reported.In this study,the HepG2 cell model was used as the main cell model in vitro.Under high lipid condition,the concentration of 50μM of Nardosinane was added to evaluate the regulation effect of Nardosinane on hepatic glucose and lipid metabolism,and the target of Nardosinane was predicted and verified.Then,C57/B6 mice were used as animal models for in vivo experiments,each group has 7 mice and they were divided into four groups :(1)control diet mice,(2)high-fat diet mice,(3)high-fat plus lowdose Nardosinane diet group(0.18g/kg Nardosinane),and high-fat plus high-dose Nardosinane diet group(0.36g/kg Nardosinane).To verify the effect of Nardosinane on liver lipid metabolism and explore its regulation of gut microbiota.The results showed that the lipid accumulation of liver cells in rat,chicken and human was decreased by Nardosinane,indicating that the lipid-lowering effect of Nardosinane was universal in multiple species.Secondly,the number of mitochondria was significantly increased,the content of mitochondrial membrane protein Cyt C was significantly enhanced,and lipid consumption was promoted,and lipid accumulation was reduced in hepatocytes.In addition,it not only alleviates liver lipid deposition induced by high fat diet,but also improves liver glutathione activity,reduces malondialdehyde content and alleviates liver oxidative stress level by enhancing liver total antioxidant capacity.Finally,from the perspective of intestinal microbiota,this study found that Nardosinane can reconstruct intestinal microbiota,reduce the abundance of harmful and obesity-marker microbiota,improve the biological function of microbiota,and inhibit lipid accumulation in the body.The combined analysis of network pharmacology and reverse target finding was used to predict and verify the regulation of lipid deposition by the effect of Nardosinane on CYP2D6.The results showed that Nardosinane could alleviate the disorder of liver lipid metabolism induced by high fat diet,reduce liver fat deposition,reconstruct gut microbiota,and alleviate the imbalance of gut microbiota.Our study not only discovered the regulatory effects of Nardosinane on lipid metabolism and intestinal microflora,but also provided a new direction for the treatment of fatty liver and other related lipid metabolic diseases in animal husbandry.Due to the wide source and low price of Nardosinane,it has laid a solid theoretical foundation for the application of Nardosinane as a feed additive for livestock and poultry.