#2366 Beneficial effects of TRIM33 on myokine-mediated renal function recovery in diabetic and obese mice

Abstract Background and Aims Myokines secreted from myocytes are related to improving metabolic diseases such as diabetes, obesity, and chronic kidney disease (CKD). Patients with diabetic kidney disease (DKD) have lower irisin levels, suggesting that a low level of irisin is a risk factor for the progression of CKD. However, it is not well known how myokines can alleviate metabolic kidney injury. This study aimed to investigate the effect of TRIM33, a negative regulator of TGF-β1 signaling, as a novel strategy to treat multiple metabolic complications simultaneously in the kidneys and muscles of obese db/db mice. Method For the in vivo experiment, five-week-old male db/db mice were assigned to three groups: db/m+, db/db, and db/db with TRIM33 plasmid mice. TRIM33 plasmid (40 μg/mice) was administered intraperitoneally. Serum glucose and myokine levels, urinary albumin excretion, renal and muscle morphology, and myokine expression in muscles were assessed. In vitro, C2C12 cells were cultivated with 2% horse serum and lipid insult in the absence or presence of TRIM33 plasmid and were analyzed for myocyte differentiation and myokines expression or production. Results TRIM33 treatment showed beneficial effects on tubular injury, tubulointerstitial fibrosis, mesangial expansion, renal dysfunction, variations in skeletal muscle fiber size and arrangement, skeletal muscle activity, and serum myokines levels in db/db mice. During the differentiation of C2C12 cells, myokine mRNA and protein expression and secretion were increased in TRIM33-transfected cells. Reduced levels of myokines expression and secretion in C2C12 cells with palmitate were improved by TRIM33 transfection. In coculture with HK-2 and C2C12 cells, increased EMT transition in TGF-b-treated HK-2 cells by coculture with palmitate-treated C2C12 cells was decreased in coculture with palmitate-treated C2C12 cells with TRIM33 transfection. Conclusion This study showed that TRIM33 is involved in the recovery of renal dysfunction via myokine in mice with diabetes and obesity.