Effects Of Trans Fatty Acids On Regulation Of Lipid Metabolism And Inflammatory Response Mediated By Intestinal Microbiome

A large number of studies have confirmed that synthetic Trans Fatty Acids(TFAs)may promote the occurrence of chronic diseases such as cardiovascular disease,atherosclerosis,coronary heart disease and type 2 diabetes.Since the intestinal microbiome plays a crucial role in human health,diet-induced disorders of the intestinal microbiome may lead to the onset of chronic diseases.This study used two types of TFA monomers to feed C57BL/6mice by filling their stomach,which concluded Elaidic acid(EA,9t-C18:1)and Linoelaidic acid(LEA,9t,12t-C18:2).Based on the inflammatory signaling pathway,intestinal microbial and metabolomic techniques,this study preliminarily explored the effects of intake of trans-fatty acid monomers of different structures on oxidative stress and intestinal microbial and lipid metabolism in C57BL/6 mice,which is helpful to understand the potential mechanism of TFAs related chronic diseases.The main research results are as follows:(1)The results of physiological parameters and lipid metabolism in mice showed that in terms of the overall trend,the intake of TFAs had no significant effect on the body weight and blood sugar of the mice.Histopathological results showed that the intake of TFAs suggested the possibility of liver deposition and hepatitis,and caused enteritis in mice.The intake of TFAs led to the up-regulation of TC and TG levels in serum and liver,the up-regulation of LDL-C and the down-regulation of HDL-C,and the more significant effect of LEA.(2)The results of key markers of oxidative stress in mice showed that the intake of TFA increased the contents of NO,TNOS and MDA in the serum,liver and small intestine of the mice,and decreased the contents of TSOD,GSH and MPO,indicating that the tissues were damaged by oxidative stress.The intake of TFAs led to up-regulation of serum and liver levels of inflammatory cytokines il-1,TNF-,and il-6 in mice,with more significant effects of LEA.Key markers of oxidative stress include key markers of oxidative stress,including nitric oxide(NO),malondialdehyde(MDA),total superoxide dismutase(TSOD),and myeloperoxidase(MPO).(3)The results of the inflammatory signaling pathway in mice showed that phosphorylation levels of IKK ? p65 and I?B? in the NF-?B signaling pathway were significantly increased and most of the p65 in the EA group and the LEA group moved into the nucleus,and the uptake of TFAs increased the p65 translocation,and the influence of LEA was more significant.These indicates that the NF-?B signaling pathway is activated.Also phosphorylation of JNK,ERK and p38 proteins related to MAPK signaling pathway induced by intake of TFAs was significantly increased and the influence of LEA was more significant,indicating that MAPK signaling pathway was activated.(4)The results of intestinal flora and short-chain fatty acids in mice showed that Firmicutes was the dominant phylum in all groups of intestinal microbes in mice,followed by Bacteroidetes and Actinobacteria.Intake of TFAs increased the abundance of Firmicutes(p<0.05),decreased the abundance of Bacteroidetes and Actinobacteria(p<0.05),and LEA was more significant.In terms of relative abundance at the family level,Lactobacillaceae was the dominant family in all groups.In the TFA group,the abundance of Lactobacillaceae increased significantly(p<0.05),the abundance of Lachnospiraceae and Prevotellaceae decreased significantly(p<0.05),and LEA was more significant.In terms of relative abundance of subordinate levels,Lactobacillus was the dominant genus in all groups.The abundance of Lactobacillus and Streptococcus increased significantly in the TFAs group(p<0.05),and the abundance of Oscillospira decreased(p<0.05),and LEA was more significant.In addition,the intake of TFAs led to a decrease in acetic acid,propionic acid and butyric acid in the faeces of the mice.(5)The results of lipidomics in mice showed that the intake of TFAs significantly decreased the levels of plasmalogen PC,phosphatidylinositols(PI),phosphatidylserines(PS),sphingomyelins(SM),sphingosinol 1-phosphate(S1P),Lyso-phosphatidylcholines(LPC)and Lyso-phosphatidylethanolamines(LPE).Levels of lipid metabolites triacylglycerols(TAG)and phosphatidylethanolamines(PE)were significantly increased,and the EA group and LEA group did not have the same degree of regulation.