Study On The Alleviation Of High-fat Diet-induced Intestinal Barrier Damage And Inflammation By Tea Polyphenols

Tea polyphenols,the major functional component of tea(Camellia sinensis),has been identified as the dominant compound for the beneficial health effects of tea.Tea polyphenols have significant anti-inflammation effect and help prevent obesity,diabetes,cancer and other diseases.Since inflammation is associated with the development of some diseases,the anti-inflammatory effect of tea polyphenols may be one of the factors for its wide-ranging health benefits.Although previous studies have observed the potential health beneficial effects of tea polyphenols and given further illustration on the molecular signal pathway,the exact mechanism underlying the anti-inflammatory effect of tea polyphenols remains obscure.Intestinal barrier is the first line of defense against intestinal microbes and food antigens.Its structural damage can lead to harmful substances such as toxins and pathogenic bacteria entering circulatory system,triggering immune responses and causing inflammation or systemic diseases.This thesis is focused on the regulating effect of tea polyphenols on high-fat diet-induced inflammation and its relationship with the intestinal barrier and gut microbiota.The main results are as follows:(1)Tea polyphenols significantly reduced high-fat diet-induced body weight gain and fat accumulation in mice.Tea polyphenols did not affect food intake,which suggested that the effects of tea polyphenols on body weight and fat accumulation were not due to reducing food consumption.The ameliorative effect of tea polyphenols on obesity was followed by the decrease of systemic and adipose tissue inflammation.Tea polyphenols inhibited high-fat diet-induced abnormal increase of serum and adipose tissue proinflammatory cytokines TNF-α,IL-1β and IL-6.(2)Tea polyphenols significantly reduced high-fat diet-induced metabolic endotoxemia,which is consistent with the regulating effect of tea polyphenols on inflammation and is related to the intestinal barrier integrity.Tea polyphenols improved high-fat diet-induced structural disorder of intestinal tissue and up-regulated the expression levels of intestinal tight junction proteins ZO-1 and Occludin.The regulation of tea polyphenols on metabolic endotoxemia and intestinal barrier integrity may be an important basis for its prevention effects of obesity-related inflammation.(3)Tea polyphenols significantly inhibited the expression of endotoxin receptors TLR4 and CD14,and their downstream key junction molecule My D88 in liver and adipose tissue,which further inhibited the degradation of IκBα and the phosphorylation activation of NF-κB.The inhibiting effect of tea polyphenols on NF-κB signaling pathway activated by endotoxin may be the reason that tea polyphenols significantly reduced proinflammatory cytokines levels in serum and adipose tissue.(4)The alleviation of tea polyphenols on intestinal barrier damage and inflammation is related to the regulating effects of tea polyphenols on gut microbiota.Tea polyphenols reduced the ratio of Firmicutes and Bacteroidetes,and restored the relative abundance of Verrucomicrobia and Proteobacteria.Tea polyphenols also increased the relative abundance of Akkermansia,Lactobacillus,Bifidobacterium,Clostridium,Intestinimonas and Sporobacter,and decreased the relative abundance of Ruminococcus,Parasutterella and Pseudoflavonifractor.The effect of tea polyphenols on the relative abundance of Akkermansia may be one of the factors that tea polyphenols maintain intestinal barrier integrity.These results suggest that tea polyphenols can alleviate high-fat diet-induced intestinal barrier damage and inflammation.Tea polyphenols can maintain intestinal barrier integrity by improving intestinal epithelial tissue structural damage and upregulating the expression level of intestinal tight junction protein Occludin and ZO-1,which further alleviate endotoxemia and inhibit the activation of TLR4/My D88 and NF-κB/IκBα signaling pathway.The alleviation of tea polyphenols on high-fat diet-induced intestinal barrier damage and inflammation is related to the regulating effects on gut microbiota.These results provide a theoretical basis and experimental reference for the underlying mechanism of tea polyphenols’ anti-inflammatory effect,and help study of dietary interventions for prevention and treatment of inflammation and its related diseases.