Mechanisms of high-glucose-induced mitochondrial damage and glycolipid accumulation in largemouth bass

The results of high-carbohydrate (HC) diets and high-glucose (HG) treatments in largemouth bass hepatocytes showed that high-glucose causes liver damage and glycolipid accumulation. High-glucose promoted the lipogenesis process by activating AMPK/ACC/SREBP-1 pathway and reduced bile acid synthesis by downregulating cholesterol 7-hydroxylase (cyp7a1) and sterol 12-hydroxylase (cyp8b1). Concurrently, HG treatments also caused mitochondrial fission and damage by increasing the expression of dynamin-related protein 1 (Drp1), leading to impaired mitochondria accumulation and mitochondria-dependent apoptosis via the p38 MAPK/Bcl-2/Casp3 pathway. Additionally, HG treatments decreased Sirt1 expression and relocated it from the nucleus to the cytoplasm, where it interacts with autophagosomes and lysosomes, inhibiting Pink1/Parkin-mediated mitophagy. This also led to the cytoplasmic translocation of Pink1 and its co-localization with Sirt1, indicating that Sirt1 regulates high glucose-induced metabolic stress by inhibiting the Pink1/Parkin mitophagy pathway. CONCLUSION: In summary, HG treatment induces mitochondrial damage and glycolipid accumulation in largemouth bass through mechanisms involving AMPK/SREBP1/ACC1-mediated lipogenesis, bile acid metabolism, Sirt-mediated mitophagy, and p38 MAPK/Bcl-2/Casp3-activated apoptosis.