Effect Of Protocatechuic Acid On Liver Inflammation Induced By High Fat And Its Mechanism

With the change of the modern way of life,a large number of high sugar and high fat diet intake can cause the body fat,lead to chronic inflammation,including metabolic inflammation,particularly in the liver,metabolic inflammation may increase the risk of liver cell immune cell infiltration,lipid accumulation and inflammatory cytokines secretion,and with the passage of time will not fade.The liver is the center of the body to regulate glucose and lipid metabolism.Inflammation will disrupt the normal metabolism of liver cells and impair insulin signal transduction.A large number of clinical studies have shown that anthocyanins can effectively reduce liver inflammation.As the main metabolite of anthocyanins in vivo,protocatechuic acid has strong anti-inflammatory activity,which can effectively prevent and reduce liver inflammation induced by high glucose and high fat diet,but the specific mechanism of action is not completely clear.Therefore,in this study,protocatechuic acid was used as the research object to investigate the effect and molecular mechanism of protocatechuic acid on the inflammation of primary hepatocytes in mice treated with high fat diet and palmitic acid.The results can provide a theoretical basis for anthocyanin-rich foods to exert anti-inflammatory activity in the body,thus preventing and reducing the metabolic inflammation caused by obesity.The main research contents and results are as follows:1.Procatechin acid reduced the phenotype of liver inflammation in mice fed with high fat diet.C57BL/6J mice were selected and fed with 60% high-fat diet to induce obesity in mice,and procatechin acid was taken as dietary supplement by gavage to explore the effect of procatechin acid on the reduction of body inflammation in mice.The results showed that a dietary supplement of 100 mg/kg/day of procatechin reduced weight and inflammation levels in the liver and blood of mice.In addition,H&E staining and oil red in the livers of fat-induced obese mice showed that fat vacuoles were caused in the high-fat group and relieved in the protocatechuic acid group.These results indicated that protocatechuic acid had a certain regulatory effect on liver inflammation and lipid accumulation in high-fat mice.2.Transcriptome sequencing studies found that differential genes were enriched in metabolic and inflammation-related pathways.Mice liver transcriptome sequencing based protocatechuic acid intervention all primary cell gene spectrum,it is using the "two-step" on mice liver perfusion,and to cultivate the primitive cells of mice liver,using saturated palmitic acid(PA)to stimulate primitive cells induced mice liver fat inflammation model was constructed,RNA-seq technology was used to perform transcriptome sequencing.The results showed that compared with the Control group,18 genes were significantly up-regulated and 29 genes were significantly down-regulated in PA group.Compared with PA group,855 genes were significantly up-regulated and 1422 genes were significantly down-regulated in PCA group.It was found that the differentially expressed genes were mainly concentrated in the pathways related to metabolism and inflammation.3.Protocatechuic acid regulates primary hepatocyte inflammation in mice through TLR4/My D88/NF-?B.100 ?mol palmitic acid was used to stimulate primary hepatocytes of mice and establish an inflammatory model to explore the molecular mechanism of protocatechuic acid on liver inflammation.The results showed that protocatechuic acid reduced the expression of inflammatory factors by regulating inflammatory signaling pathways.In addition,TLR4 was silenced by si RNA technology,which confirmed that protocatechuic acid regulates the signal transfection of inflammatory signaling pathway through TLR4/My D88/NF-?B,thereby improving liver inflammation.In summary,procatechin acid can reduce inflammation through the TLR4/My D88/NF-?B pathway,thereby increasing insulin sensitivity and restoring normal liver metabolism,which provides a theoretical basis for further elucidations of the anti-inflammatory activity of procatechin acid and other natural products in the body and the prevention and reduction of liver inflammation caused by obesity.To lay the theoretical foundation for preventing and reducing metabolic inflammation caused by obesity.