Stankova 2018 MiP2018
Nonalcoholic fatty liver disease (NAFLD) can be considered the hepatic manifestation of the metabolic syndrome and is closely associated with obesity and insulin resistance. NAFLD represents the most common chronic liver disease and encompasses a range of pathologies from steatosis, nonalcoholic steatohepatitis (NASH), fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. Mitochondrial dysfunction is crucial to the pathogenesis and progression of NAFLD. The cafeteria diet reflects the variety of highly palatable and energy dense foods in Western countries. The aim of this work was to induce NAFLD/NASH in mice fed by Western-style diet and evaluate its effect on liver mitochondrial functions.
Experiments were performed on male C57Bl/6J mice fed ad libitum by standard control diet (CD, PicoLab RD 20, LabDiet) and tap water or Western diet (WD, AIN-76A WD, TestDiet) and glucose-fructose syrup for 24 weeks. Liver plasma enzymes and histological changes of liver tissue (Hematoxylin-eosin, Sirius red) were evaluated. Mitochondrial respiration of liver tissue homogenates was assessed by high-resolution respirometry (Oroboros Oxygraph-2k) using SUIT reference protocols and ROS production was measured using CM-H2DCFDA (Tecan Infinite M200).
Mice reared on WD diet gained significantly more weight and their liver weight (both absolute and relative) were significantly higher in comparison to mice on CD. Histologically, Western diet induced mixed steatosis, moderate inflammation and mild perisinusoidal fibrosis. We have found a decrease in respiration activated by succinate in both OXPHOS and ET states. NADH-dependent respiration, octanoylcarnitine activated respiration, maximal ET and OXPHOS capacities and ROS production were not significantly affected. Our results demonstrating changes in mitochondrial functions could be very interesting and important, especially with regard to the recent discovery of the role of succinate as signaling molecule and the role of succinate dehydrogenase in inflammation-linked pathologies.
This work was supported by research program PROGRES Q40/02 and Inter-Cost LTC17044
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Obesity, Other
Organism: Mouse Tissue;cell: Liver Preparation: Homogenate
Coupling state: OXPHOS, ET Pathway: F, N, S HRR: Oxygraph-2k
- Dept Physiology, Fac Medicine Hradec Králové, Charles Univ, Czech Republic. – [email protected]