Effects Of Meat Proteins In High-fat Diets On Intestinal Barriers And Liver Pathology Of Mice

Protein is one of the essential nutrients,and meat is an important source of highquality protein.In recent years,the relationship between dietary proteins,fats and health has attracted more and more attention.There are a lot of researches on diet and health,including dietary protein,dietary fiber,high and low fat.The colonic mucosa provides a vital defensive barrier separating the body from the microbial populations residing in the intestinal lumen.The loss of barrier integrity increases the translocation of bacterial antigens and stimulates inflammation in the intestinal mucosa,which is the central pathological feature of inflammatory bowel disease(IBD)in colon and further nonalcoholic fatty liver disease(NAFLD)in Liver.This thesis focuses on how intestinal mucus and intercellular tight junctions(TJs)act together to maintain the integrity of the colonic barrier and how barrier integrity is dysregulated in response to different meat protein diets in normal and diet induced obese conditions.The main findings are as follows:1.Effects of protein diets intake from soybean,chicken and pork sources on body weight,growth performance and physiological indexes of miceIn order to explore the influence of different meat proteins on the physiological response of mice;soybean,chicken and pork proteins either with low fat(12%Kcal)or high fat(60%Kcal)were administered to C57BL/6J mice for 12 weeks.Body weight and daily food intake were measured during the whole feeding period.After the end of the experiment,the changes in body weight,feed intake,organ index(liver,epididymal adipose),colonic cytokines expression and blood biochemical parameters of mice in different diet groups were compared.The results showed that high fat meat proteins increased body weight as well as body weight gain of mice.Mice fed high fat pork(HFP)had significantly heavier body weight than those fed high fat soy(HFS)and high fat chicken(HFCH).In high fat diet pork proteins diet increased the weight of liver significantly.High fat diet groups significantly increased epididymal adipose tissue weight in comparison with low fat diet(LFD),which may be correlated to feed intake and weight gain.In high fat diet(HFD)fed mice,intake of meat protein diets caused higher IL-1?,but lower TNF-? and IL-22 indicating that intake of chicken and pork proteins might compromise innate immunity combined with inflammation in colon.High-fat meat protein diet upregulated several key cytokines along with elevation in IL-1 ?,TNF-?,IL-6 and IFN? concentrations in serum.In summary,compared with the low fat soybean group,the meat protein groups are more effective in promoting growth of mouse.Compared with the low fat group,the meat protein groups in high fat are more likely to cause fat deposition.These results suggest that dietary proteins have significant effects on the physiological status and growth performance of mice.2.Effects of meat proteins in high-fat diet on intestinal barriers and tight junction proteins in miceThe mice were fed for 12 weeks and then the histological and morphological changes,goblet cells,Muc2 expression and tight junction proteins in the colon were measured.The study aimed to illustrate the specific impacts of soybean,chicken and pork meat proteins on mice colonic intestinal barrier in either low or high fat groups.Intake of high-fat pork protein diet decreased number of goblet cells and inhibited Muc2 expression in colon,which impaired mucus barrier.Immunohistochemistry indicated decreased crypt depth and downregulation of tight junction proteins in high-fat diet fed mice signifying losses of epithelial barriers.Increased epithelial cell proliferation indicated by Ki-67 was observed in colon of HFD mice that were fed chicken and pork proteins in comparison with soybean protein fed mice.In addition,pork protein diet reduced the key zonula occluden-1 and Ecadherin proteins.Intake of high-fat meat protein diets resulted in the impairment of colon barrier through mucus suppression,down-regulation of tight junctions,and gut inflammation in mice.3.Gut inflammation and vascular barrier impairment exacerbates hepatic injury in mice in response to high fat meat proteins dietsTo evaluate the effects of intestinal dysfunction and gut barrier impairment on liver pathology and injuries like NAFLD,mice were fed with soybean,chicken and pork protein diets in either HFD or LFD for 12 weeks and monitored for liver and colon pathology and injury progression,especially attention to the GVB dysfunction.The H&E staining showed a large amount of fat vacuoles and disorganized structures in the liver in HFD-fed mice.High fat pork and chicken showed more lipid droplets confirming the increased hepatic lipid accumulation as demonstrated by Oil Red O staining.In accordance with the histology results,the mRNA expression of hepatic proinflammatory cytokines,IL-1?,TNF-? and MCP-1,were markedly increased in meat proteins fed HFD mice,which indicated severer liver injury and inflammation relative to LFD fed mice.Plasma endotoxin(LPS)indicated a trend of elevation in circulatory endotoxin levels in high fat chicken and pork protein fed mice relative to soy bean protein and also to the LFD fed mice.Further the gene expression of pattern recognition receptor for bacterial components in the liver,such as TLR4 and TLR9,were significantly upregulated in high fat chicken and pork protein fed mice compared with the soybean group.In summary gut inflammation exacerbates liver injury and fibrosis in HFD mice,which may contribute to the development of NASH.Beyond the damaged intestinal epithelial barrier,GVB disruption with bacterial translocation may play a key role in the pathogenesis of liver.