The Study Of Effects And Mechanisms Of Dimethyl Fumarate On Obesity-related Glomerulopathy

Background: In obesity patients,there are multiple organ lipid deposits.Excessive lipid deposition in kidney tissue causes damage to various intrinsic cell functions such as podocytes and renal tubular epithelial cells,which is called Obesity-related glomerulopathy.The main mechanism may be related to the excessive lipid deposition in kidney tissue leads to oxidative stress and increase the level of proinflammatory cytokines.Nrf2 is an important transcription factor regulating oxidative stress in cells.It not only balances intracellular redox reactions but also inhibits NF-κB activity and alleviates inflammatory responses.Dimethyl fumarate(DMF)is a specific activator of Nrf2,the role and specific mechanism of in obesity-related nephropathy is still unclear.Objective: The role and molecular mechanism of DMF in obesity-related glomerulopathy were further explored by constructing a high-fat fed mouse model and administering DMF.Methods: SPF-class 8-week-old C57BL/6J mice were divided into control group,high-fat group,high-fat+DMF group according to feeding conditions,and urine,blood and kidney tissues were collected at week 14.Observe the trend of body weight,the weight of kidney and epididymal fat,detect the level of urinary albumin and blood lipids,observe the pathological changes of kidney tissue and lipid infiltration,and detect the expression of oxidative stress related proteins,proinflammatory cytokines and lipid metabolism.Results: Compared with the control group,the mice in the high-fat group had significantly increased body weight,proteinuria,elevated blood lipids,glomerular hypertrophy,tubular vacuoles,renal interstitial inflammatory cell infiltration,and lipid deposition in the renal tubules.Compared with the high-fat group,the mice in the high-fat+DMF group had decreased body weight,decreased the level of urinary protein and triglyceride,kidney tissue pathological damage has been alleviated and reduce the infiltration of renal tubular lipids.The expression of proinflammatory cytokines such as TNFα and IL-6 was decreased,and the expression of Nrf2 and downstream proteins was increased.Conclusion: Dimethyl fumarate can reduce lipid deposition by alleviating inflammatory response and oxidative stress,thereby improving kidney damage in obese mice.