Riboflavin ameliorates pathological cardiac hypertrophy and fibrosis through the activation of short-chain acyl-CoA dehydrogenase

Short-chain acyl-CoA dehydrogenase (SCAD), the rate-limiting enzyme for fatty acid I3-oxidation, has a negative regulatory effect on pathological cardiac hypertrophy and fibrosis. FAD, a coenzyme of SCAD, participates in the electron transfer of SCAD-catalyzed fatty acid I3-oxidation, which plays a crucial role in maintaining the balance of myocardial energy metabolism. Insufficient riboflavin intake can lead to symptoms similar to short-chain acylCoA dehydrogenase (SCAD) deficiency or flavin adenine dinucleotide (FAD) gene abnormality, which can be alleviated by riboflavin supplementation. However, whether riboflavin can inhibit pathological cardiac hypertrophy and fibrosis remains unclear. Therefore, we observed the effect of riboflavin on pathological cardiac hypertrophy and fibrosis. In vitro experiments, riboflavin increased SCAD expression and the content of ATP, decreased the free fatty acids content and improved PE-induced cardiomyocytes hypertrophy and AngII-induced cardiac fibroblasts proliferation by increasing the content of FAD, which were attenuated by knocking down the expression of SCAD using small interfering RNA. In vivo experiments, riboflavin significantly increased the expression of SCAD and the energy metabolism of the heart to improve TAC induced pathological myocardial hypertrophy and fibrosis in mice. The results demonstrate that riboflavin improves pathological cardiac hypertrophy and fibrosis by increasing the content of FAD to activate SCAD, which may be a new strategy for treating pathological cardiac hypertrophy and fibrosis.

Automated summary

Short-chain acyl-CoA dehydrogenase (SCAD), an enzyme involved in fatty acid oxidation, regulates pathological cardiac hypertrophy and fibrosis. Its coenzyme FAD plays a crucial role in myocardial energy metabolism. Insufficient riboflavin intake can lead to symptoms similar to SCAD deficiency or FAD gene abnormalities, but the effect of riboflavin on cardiac hypertrophy and fibrosis is unclear. In this study, riboflavin was found to increase SCAD expression, ATP content, and FAD content, while decreasing free fatty acids. This led to improvements in induced hypertrophy and fibrosis in cardiomyocytes and cardiac fibroblasts. In animal experiments, riboflavin improved TAC-induced hypertrophy and fibrosis by increasing SCAD expression and energy metabolism. These findings suggest that riboflavin may be a potential treatment for pathological cardiac hypertrophy and fibrosis.