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

Abstract

The mechanistic link between obesity and renal failure has been proposed to involve mitochondria reactive oxygen species generation and lipotoxicity. These pathological conditions make mitochondria of 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 a rat model of intra-abdominal obesity and renal damage induced by a high-sucrose diet. Mitochondria from sucrose-fed (SF) kidneys in the presence of pyruvate-malate generated H2O2 at a higher rate than from control (79.81 ± 4.98 vs. 65.84 ± 1.95 pmol·min−1·mg protein−1). 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−1·mg protein−1). However, cytochrome c release from SF kidney mitochondria was lower than from control. In addition, cardiolipin, a mitochondria-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 and light chain 3-B, as autophagy protein markers, and caspase-9, as apoptosis protein marker, were found decreased in SF kidneys. 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.

Are fat and sugar just as detrimental in old age?

“…Consuming 30%g/vol fructose in drinking water for 5.5 months led to a 20% increase in body mass as a result of intra-abdominal fat expansion compared to chow-fed young rats [30]. Consuming 30%g/vol sucrose in drinking water also increased hydrogen peroxide generation and lipid peroxidation in the kidney [31]. Another study comparing the effects HFD and HSD (both 30%g/g or g/vol) found that despite both diets inducing similar weight gain (12%) and similar levels of hepatic fat content after 8-12 months, only HSD-induced hyperleptinemia and hyperinsulinemia in addition to increased lipogenic gene expression like sterol regulatory element-binding transcription factor 1 (SREBP1) and peroxisome proliferator-activated receptors gamma (PPARλ) increased nitrosylation of mitochondrial proteins, and increased expression proteins involved in mitochondrial fission like dynamin-related protein 1 relative to fusion protein mitofusin [32].…”

Apigenin ameliorates oxidative stress and mitochondrial damage induced by multiwall carbon nanotubes in rat kidney mitochondria

“…Previous research has shown that there is a link between mitochondrial dysfunction and kidney failure. [32][33][34] Kidney energy (adenosine triphosphate [ATP]) demand for normal functions is high.…”

Activity of Kidney Mitochondrial Nad+-Dependent Dehydrogenases in Rats Under Conditions of Different Nutrient Supply

“…Показано, що дисфункція мітохондрій, що виникає внаслідок порушення регуляції роботи дихального ланцюга, зниження мембранного потенціалу, супроводжується зменшенням вмісту АТФ та інтенсифікацією генерації АФК, що сприяє пошкодженню нирок (Bhatia et al, 2020;Ruiz-Ramírez et al, 2020). У нормі в нирках біля 90 % АТФ, необхідної для реабсорбції глюкози, іонів та метаболітів, утворюється шляхом окисного фосфорилювання (Braga, et al, 2022), при цьому дисбаланс процесів енергоутворення в першу чергу буде супроводжуватися порушенням реабсорбційної та фільтраційної здатності нирок.…”