Different Lipidomic Signatures between proximal and distal adipose tissue in diabetic nephropathy

Abstract

Abstract Perinephric adipose tissue (PRAT) is a component of visceral adipose tissue that is considered an important factor in maintaining renal homeostasis. PRAT has a close relationship with the kidney. Under metabolic dysfunction, PRAT inflammation may precede the damage of blood sugar to the kidney. Whether there is a difference between proximal and distal lipids of PRAT and its significance are not clear. For this reason, we used the nontargeted absolute quantitative method for lipid analysis. The nontargeted analysis method can distinguish various types of lipids in a sample. Absolute quantification of lipids against an internal standard can not only determine the difference in lipid levels between groups but also yield the absolute concentration of lipids in each group. Therefore, we compared the amount and lipid level of PRAT between diabetic kidney disease (DKD) mice and nondiabetic mice and the difference in the lipid spectrum between proximal (within 5 mm from the kidney) and distal (outside 5 mm from the kidney) PRAT in DKD mice. The results showed that DKD mice had significantly more PRAT than the control group. Lipid proteomics found that PRAT in the DKD group significantly differed from that in the control group in glycerides, sphingolipids and phospholipids. Glycerides, including TG (41:10e), TG (43:4), TG (45:7e), TG (52:6) and TG (71:5), were significantly upregulated in PRAT of DKD mice, while TG(56:8e) and TG(55:1) were downregulated. The sphingolipids cer(d36:2), cer(d36:1), cer(d34:2), cer(d34:1) and cerP(t39:3) and the phospholipids PC (38:4), PS (36:4), PS(38:4), PI(42:0), CL(85:1) and CL(76:6) were significantly upregulated in the PRAT of the DKD mice, whereas LPE(16:1e) and PG(41:0) were significantly downregulated. TG(38:3), TG(50:5), TG(52:12e) and TG(56:9e) in the proximal end of PRAT in the DKD group were higher than they were in the distal end, especially TG(38:3), but the sphingolipids and phospholipids in the proximal end of PRAT in the DKD group were downregulated. Our results show that the amount and lipid level of PRAT are significantly higher in DKD mice than non-DKD mice, and there are differences between proximal and distal PRAT. Lipid metabolism in the perirenal fat microenvironment may be related to DKD. These new insights into the mechanism of DKD may be helpful for developing therapeutic strategies for this disease.