The lipidome of the kidney tubules of ob/ob mice is affected at the infralesional level

Whether changes in tubular lipidomic composition precede the onset of observable kidney damage in obesity is unknown. We manually isolated the proximal convoluted tubule (PCT), the cortical thick ascending limb of Henle's loop (cTAL) and the cortical collecting duct (CCD) from five lean and five ob/ob mutant mice that have a defect in the leptin gene and subjected them to lipidomic analysis by high-resolution mass spectrometry acquisition. In total, more than 700 molecular species of glycerophospholipids (including cardiolipins and peroxidised phospholipids) and sphingolipids were identified and analyzed. Significant compositional differences were observed between the three tubular segments, which serve as true signatures associated with obesity. The fatty acid composition of triglycerides, phospholipids and cardiolipins was significantly altered by leptin deficiency and these changes were predominantly observed in the polyunsaturated fatty acid (PUFA) composition and showed different patterns in different tubular segments. This resource provides unparalleled details of the lipid composition of tubular segments, thereby enhancing our understanding of the tubular metabolic and lipidomic reprogramming that occurs at the earliest stages of nephropathy associated with obesity in ob/ob mice.