Lipotoxic Nephropathy Is More Severe in Male than Female Rats N with Non-Insulin Diabetes Mellitus (NIDDM)

. Dyslipidemia is a prominent risk factor for nephropathy in NIDDM; as indicated by longitudinal studies (1,2). This association is not surprising, as the most severe examples of hypercholesterolemia are either familial, or caused by NIDDM (3). Moreover, dyslipidemia in NIDDM is also coupled with markedly increased levels of oxidized LDL (oxLDL) (4), and heightened oxidative stress is recognized to complicate NIDDM (5). However, specific renal toxicity of lipid oxidant (lipotoxicity) is not proven in NIDDM, perhaps because such proof is difficult to obtain in human investigations. We tested the hypothesis that lipotoxicity enhances the level of glomerular oxidized LDL receptor 1 (OLR1) in obese males rats with NIDDM, augmenting oxidant stress and resulting fibrosis.