Prevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy

SPECIFIC AIMSThere has been a long debate about the reversibility of diabetic nephropathy, and the problem has been difficult to approach because of the lack of suitable animal diabetic nephropathy models closely resembling human diabetic glomerulosclerosis. We investigated and evaluated whether renal injury in a mouse model of lipoatrophic diabetes (A-ZIP/F-1 mice; A-ZIPTg/+) is consistent with clinical diabetic nephropathy. We examined whether leptin is effective in the prevention or treatment of renal injury in A-ZIPTg/+.PRINCIPAL FINDINGS1. Characteristics of renal injury in A-ZIP/F-1 miceLipoatrophic diabetes is a disorder characterized by paucity of adipose tissue, severe insulin resistance, and elevated triglycerides. A-ZIPTg/+, which express a protein that inactivates basic-zipper transcription factors in adipose tissue under the control of aP2 promoter, have been reported to exhibit severe lipoatrophic diabetes. Histological analysis revealed marked glomerular hypertrophy and mesangial expansion ...