Kidney dysfunction induced by sucrose-rich diet in rat involves mitochondria ROS generation, cardiolipin changes and the decline of autophagy protein markers.

The mechanistic link between obesity and renal failure has been proposed to involve mitochondria reactive oxygen species (ROS) generation and lipotoxicity. These pathological conditions make mitochondria of a particular interest in the regulation of cell function and death by both apoptosis and autophagy. Therefore, this work was undertaken to investigate mitochondria function, autophagy and apoptosis protein markers in the kidney from rat model of intra-abdominal obesity and renal damage induced by high sucrose diet. Mitochondria from sucrose fed (SF) kidney in the presence of pyruvate/malate generated hydrogen peroxide (H₂O₂) at a higher rate than from control (79.81 ± 4.98 vs 65.84 ± 1.95 pmol/min/mg protein). With succinate, the release of H₂O₂ was significantly higher compared with pyruvate/malate and it remained higher in SF than in control mitochondria (146.4 ± 8.8 vs 106.1 ± 5.9 pmol/min/mg protein). However, cytochrome c release from SF kidney mitochondria was lower than from control. In addition, cardiolipin, a mitochondrial-specific phospholipid was found increased in SF mitochondria due to the enhanced amount of both cardiolipin synthase and tafazzin. Cardiolipin was also found enriched with saturated and monounsaturated fatty acids which are less susceptible to peroxidative stress involved in cytochrome c release. Furthermore, Beclin-1, LC3-B, as autophagy protein markers, and caspase 9 as apoptosis protein marker, were found decreased in SF kidney. These results suggest that the decline of autophagy protein markers and the lack of apoptosis process could be a pathological mechanism of cell dysfunction leading to the progression of renal disease in SF rats.