| Background and Objective:NAFLD(non-alcoholic fatty liver disease),is one kind of clinical pathology syndrome,with excessive fat storing in liver caused by various reasons instead of heavy alcohol and characterized by fatty degeneration of liver cells and the accumulation of lipid.NAFLD,closely related to the occurrence and the progression of liver cirrhosis and hepatoma,is becoming one of the most important health problems around the world.In the early phase of the disease,it is necessary to actively explore a safe and effective intervention measure which can dramatically improve the patient's life quality and reduce the medical burdens of countries.Sports are world widely recognized as the most convenient,safe,economic and effective approach of prevention and treatment of NAFLD,meanwhile,are the ideal solution to early and mid-term NAFLD outcomes.Despite the fact that multiple population studies have shown that moderate endurance exercise can be an effective management of NAFLD and animal experiments have revealed that exercises can reduce inflammation,injury and fibrosis of liver through inhibiting of macrophage infiltration,the specific mechanism is still not clear.Effects of exercise on NAFLD,may be a direct function but more likely to be an indirect function through the interaction among the different tissues of the body.Intestine is the central link in the occurrence and development of system inflammation and metabolic syndrome.There is a close relationship between NAFLD and gut barrier function,which plays an important physiological,physics,chemistry and immunological effect both in nutrient absorption and preventing of harmful molecules into body.The damage of intestinal barrier function with the increased leakage of gut derived antigens(such as LPS)may lead to visceral lipid deposition.Studies have shown that NAFLD patients were often accompanied with intestinal dysbacteriosis and increased intestinal permeability further influence liver fat distribution.Gut microbiome is a major metabolic organ in body,playing an important role in the pathogenesis of NAFLD.Liver received 70% blood via the portal sent by intestinal,in consequence that liver become the first defense line against intestinal bacteria antigen and also one of the most widely exposed organ to gut toxins and metabolites.Directly or indirectly,the change of intestinal microbiome and their metabolites can affect the inflammatory of the host and further change the metabolic balance of body.The key end products of colonic fermentation are the SCFAs-butyric,acetic and propionate.Acetate can be absorbed and utilized by peripheral tissues.Acetate increases the formation of cholesterol which could be inhibited by propionate.Propionate can be absorbed primarily by the liver and it seems possible that one of the determinants of the actions of propionate on serum lipids is the ratio of propionate to acetate.Declining of this ratio is associated with reductions in serum lipids through which the risk of cardiovascular disease can be further reduced.Butyrate is the preferred energy source of colonocytes and has been implicated in the control of the machinery regulating apoptosis and cellular proliferation and differentiation.Increased intestinal permeability and disruption of the mucosal barrier are required for microbial products to translocate from the intestinal lumen to extra intestinal space.This study established a C57BL/6 mice model of NAFLD using high fat diet.Meanwhile,we trained these mice with treadmill as an intervention.We observe the influence of exercises on intestinal mucosal barrier function,gut microbiome with their metabolic products-the content of short fatty acids and liver lipid accumulation as well as inflammation.From the perspective of intestinal barrier function and gut microbiome composition,we explore the potential mechanisms of that hepatic lipid accumulation and inflammation of mice with high fat diet were alleviated through exercises in order to provide a new train of thought for mechanisms study of NAFLD.Methods:C57BL/6 mice were divided into three groups that received a normal diet(ND)plus sedentary,a high-fat diet(HFD)plus sedentary,and a HFD plus exercise training(HFD-EX).Mice in the HFD-EX group were trained on a treadmill.After eight weeks,the content of general biochemical and inflammation cytokines in plasma and liver were tested.Liver tissues were observed by HE Staining and Oil Red O Staining.Intestine tissues were observed by transmission electron microscope.Structures and clusters of gut microbiome were analyzed by DGGE maps.The content of short chain fatty acid in mice faeces were determined by GC.Results:Compared with ND group,the contents of plasma T-CHO,TG,LDL-C,hepatic TG,T-CHO and the expression levels of TLR4?TNF-? and IL-6 in liver of HFD group were significantly increased(P<0.05)and the expression level of Occludin in colon tissues was decreased(P<0.05).Compared with HFD group,the contents of plasma TG,LPS,FBG,hepatic TG,T-CHO and the expression levels of TLR4?TNF-? and IL-6 in liver of HFD-EX group were significantly decreased(P<0.05)and and the expression level of Occludin in colon tissues was increased(P<0.05).The content of short chain fatty acid in mice showed that,compared with ND group,the content of acetic,propionate,and butyrate in mice faeces of HFD group and HFD-EX group were remarkably decreased(P<0.05).Although structures of gut microbiome in each group were showed totally different by analysis of their DGGE maps,the DGGE maps of HFD-EX group is much more similar with ND group.The mRNA relative quantification of Proteobacteria,Actinobacteria,Bacteroidetes and Firmicutes in mice faeces showed that,compared with ND group,the level of Firmicutes m RNA were lowed in HFD group(P<0.05);compared with HFD group,the level of Actinobacteria mRNA were elevated in HFD-EX group(P<0.05).Pathology tests of liver tissues indicated that the accumulation of fat vacuoles and lipid droplets were significantly increased in HFD group compared with ND group and decreased in HFD-EX group compared with HFD group.Intestine Tissues under transmission electron microscope demonstrated that the intestine epithelium microvilli were reduced and the width of tight junction structures were widen in HFD group compared with ND group meanwhile the intestine epithelium microvilli were increased and the width of tight junction structures were narrowed in HFD-EX group compared with HFD group.Conclusion:Exercise training reduces hepatic fat accumulation and inflammation in high-diet fed mice possibly by reconfiguration of their gut microbiome. |
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