The Mitochondrial Trigger in an Animal Model of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial beta-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy's decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD.

Automated summary

The study demonstrates the significance of mitochondrial oxidative stress and sequential organelle dysfunction in an obesogenic diet animal model of NAFLD. All diets induced marked mitochondrial oxidative stress and decreased mitochondrial DNA content, leading to impaired mitochondrial biogenesis and reduced autophagy. The supplementation of DHEA did not prevent the diet-induced changes.