Cyanidin-3-O-arabinoside restores fatty acid oxidation and mitochondrial function, improving HFD-induced glucose and lipid disorder in mice.

High-fat diet (HFD) consumption is a primary driver of glucose and lipid metabolism disorder (GLMD), leading to conditions like non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. These disorders are characterized by impaired fatty acid oxidation (FAO) and mitochondrial dysfunction, exacerbating metabolic imbalances. Current therapeutic strategies often have side effects or limited efficacy, prompting research into natural compounds. Cyanidin-3-O-arabinoside (C3A), a flavonoid from Big Fruit Hawthorn peel, has shown promise in attenuating weight gain and adipogenesis, making it a candidate for addressing GLMD by targeting fundamental metabolic pathways.

Mice were fed a high-fat diet (HFD) for 8 weeks to induce glucose and lipid metabolism disorder (GLMD). Following this, mice were treated with Cyanidin-3-O-arabinoside (C3A). To investigate the role of CD36, some mice received AAV8-TBG for CD36 overexpression. Researchers evaluated blood glucose, blood lipid (TC, ALT), and liver injury status. Liver steatosis and fatty acid oxidation (FAO) were assessed via pathological staining and Western blot. Mitochondrial function was analyzed using transmission electron microscopy and specific kits, while CD36/AMPK/PGC-1α protein expression was detected to elucidate the underlying mechanism.

C3A significantly reduced fasting blood glucose (FBG), total cholesterol (TC), and alanine aminotransferase (ALT) levels, indicating improved systemic glucose and lipid homeostasis and reduced liver injury. Pathological staining confirmed a significant reduction in hepatocyte steatosis and oil red O-stained lipid droplets, directly demonstrating C3A's protective effect on liver health. The study observed a promotion of FAO-related proteins, alongside a significant increase in the number of mitochondria, ATP content, and OXPHOS levels, collectively pointing to restored mitochondrial function and enhanced energy metabolism.

C3A activated the CD36/AMPK/PGC-1α pathway, which was identified as crucial for improving HFD-induced FAO damage and mitochondrial dysfunction.

However, when CD36 was overexpressed using AAV8-TBG, the beneficial effects of C3A on abnormal glucose and lipid metabolism, FAO damage, and mitochondrial dysfunction were notably weakened. This suggests that CD36 plays a critical role in mediating C3A's therapeutic actions, and its dysregulation can compromise the compound's efficacy.