Effects Of High-fat Diet And Short-chain Fatty Acids On Gastric Mucosa In Mice

Objective:To investigate the the expression of core proteins Last1(Large tumor suppressor gene 1),Mst1(Mammalian infertility 20-like kinase 1),Yap1(Yes-associated protein 1)of the hippo signaling pathway and CDX2(Tail-type homeobox transcription factor 2),CDK2(Cyclin-dependent protein kinase 2),Ki-67(Cell-associated nuclear antigens)in the gastric mucosa of high-fat diet mice and whether different SCFAs(short-chain fatty acids)interfering with the expression of the above indicators in the gastric mucosa of high-fat diet mice.Ultimately to explore whether high-fat diet promotes the occurrence of gastric mucosal lesions,and whether short-chain fatty acids are protective factors for gastric mucosa.Methods: Use 50 C57 BL / 6 male mice,randomly divided into 5 groups and then fed different feeds,According to the different feeding diets,they were divided into normal diet group,high-fat diet group,high-fat + acetic acid diet group,high-fat + propionic acid diet group,High fat + butyric acid diet group.The mice in the normal diet group were fed with normal diet(10% of energy was derived from fat,3.85 kcal / gm).The high-fat diet group was fed with high-fat diet(60% of energy derived from fat,5.42 kcal / gm).In addition,on the basis of high-fat feed,185 g of sodium acetate,215 g of sodium propionate,and 250 g of sodium butyrate were respectively added to 5000 g high-fat feed,then a food processor was used to form a food bar of 50-60 g at 300 rpm and sterilized breeding,group names are high-fat + acetic acid diet group,high-fat + propionic acid diet group,high-fat + butyric acid diet group.After 16 weeks of feeding,weigh and record the weight of each group of mice,use HE staining(hematoxylin-eosin staining)to observe histopathological of gastric mucosa in mice,and then take gastric mucosa tissue for Immunohistochemistry,Western blot,and Real-time PCR to detect Last1,Mst1,Yap1,CDX2,CDK2,Ki-67 expression.Results:(1)Comparison of body weight between mice in each group: The weight of mice in the high-fat group was significantly higher than other groups(P< 0.05),and there was no significant difference in body weight between the other groups of mice(P> 0.05).(2)HE staining results: There was no significant difference in histopathological of mice in each group,they are normal gastric mucosa and in which we can see no inflammatory cell infiltration,no intestinal metaplasia,no abnormalities such as cell dysplasia and cancer cell infiltration.(3)Expression of Hippo-Yap pathway core proteins Last1,Mst1,and Yap1 in mice in each group:Last1,Mst1 expression was higher in the normal diet group,high fat + acetic acid diet group,high fat + butyric acid diet group than fat diet group,high fat + propionate group,and the difference was statistically significant(P< 0.05),And there was no statistical difference between the other groups(P> 0.05);In contrast to Last1 and Mst1 expression,Yap1 expression in the high-fat group,high-fat+ propionic acid diet group was higher than that in the normal diet group,high-fat +acetic acid diet group and high-fat + butyric acid diet group,and the difference was statistically significant(P< 0.05),There was no significant difference between the other groups too(P> 0.05).(4)Expression of CDX2,CDK2 and Ki-67 in mice in each group: CDX2,CDK2,and Ki-67 expression in the high-fat group,high-fat + propionic acid diet group was higher than the normal diet group,high-fat + acetic acid diet group and the high fat + butyric acid diet group,and the difference was statistically significant(P <0.05),There was no significant difference between the other groups(P> 0.05).Conclusion:(1)High-fat diet can inhibit the expression of Last1 and Mst1 in gastric mucosal,promote the expression of Yap1,promote the imbalance of Hippo-Yap pathway,thus promoting the occurrence and development of gastric mucosa lesions.(2)High-fat diet can raise the expression of CDX2,CDK2 and Ki-67 in gastric mucosa of mice,thereby promoting the development of gastric mucosal lesions.(3)Acetic acid and butyric acid in short-chain fatty acids can prevent the gastric mucosa from being damaged by high-fat diet,and have a protective effect on the gastric mucosa of mice.So they are considered to be protective factors against damage of gastric mucosa,but propionic acid has no protective effect.