Dietary vitamin B6 and the pathophysiology of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition often linked to metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. NAFLD can progress to more severe conditions like non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. While lifestyle changes are currently the main therapeutic strategy, emerging evidence suggests that dietary micronutrients, such as vitamin B6, could play an important role in the development and progression of NAFLD through their involvement in one-carbon (1C) metabolism. This study aimed to explore the impact of dietary vitamin B6 deficiency on NAFLD progression using a high-fat high-sugar (HFHS) diet-induced mouse model. Thirty-two male C57Bl/6J mice were randomly assigned to four dietary groups with varying levels of vitamin B6. The study evaluated physical parameters, clinical markers, liver and fecal metabolites, and gut morphology after eight weeks of dietary intervention. Our findings demonstrated that vitamin B6 deficiency significantly influenced liver B6 levels, lipid accumulation, and key metabolites in the 1C metabolic pathway. Notably, animals in the vitamin B6 deficiency group exhibited reduced plasma triglyceride levels, elevated liver triglyceride content, and alterations in homocysteine and glycine levels, indicating disruptions in both lipid and 1C metabolism. Interestingly, fecal tryptophan metabolism was also impaired in these animals. These findings suggest that dietary vitamin B6 plays a crucial role in regulating NAFLD progression, particularly in the context of diet-induced NAFLD, providing insights into potential dietary interventions for disease management.