THE METHIONINE RESTRICTION DIET ATTENUATES CHRONIC KIDNEY PROGRESSION IN MICE.

Abstract Background and Aims The clinical usefulness of protein-restricted diets is known to slow the progression of obesity, fatty liver, aging and cancer. Protein-restricted diet in chronic kidney disease is known to alleviate the deterioration of the renal function. The purpose of this study is to confirm whether the reduction in new function can be improved when methionine restricted (MR) diet is supplied in the chronic kidney disease (CKD) animal model and to study the its renoprotection mechanism. Method We used four-week-old C57L/B6 to make a CKD model by administration 0.025% adenine chow mixed with R3 diet for four weeks for the control group. For the MR diet group, we supplied the mixture of 0.025% adenine with methionine/Choline Deficient Diet. We measured serum blood urea nitrogen (BUN), serum creatinine, gut permeability, stool short chain fatty acid (SCFA), kidney α-SMA and renal pathology. This study was approved by Korea University Institutional Animal Care and Use Committee (KOREA-2019-0047). Results The principal coordinates analysis of the microbiome showed the two groups have distinctive component features. The stool SCFA, especially butyrate was increased in the MR diet group. However, gut permeability using FITC-dextran showed no significant change. The kidney α-SMA and MT stain area showed that the MR diet could improve renal fibrosis. The kidney inflammation including neutrophil and macrophage infiltration was also improved in histology analysis. The macrophage phenotype was more favorable to M2 type. Serum BUN and creatinine were significantly attenuated in the MR diet group. Conclusion In conclusion, the MR diet has a reno-protective effect in adenine induced CKD. The MR diet increased butyrate production and decreased renal inflammation and fibrosis. These results shed light on the role of protein restriction diet for CKD management in the real world.