Abstract
The potent hepatotoxic mycotoxin rubratoxin B causes fatty liver. To elucidate the lipid accumulation mechanism, we investigated the type of lipid droplets accumulated and the activities of the lipogenic enzymes glucose-6-phosphate dehydrogenase (G6PD) and fatty acid synthase in mouse livers treated for 24 h with rubratoxin B. Oil Red O staining revealed numerous microvesicular lipid droplets in the liver cells of rubratoxin B-treated mice. In addition, treatment with rubratoxin B notably induced the activity of G6PD, a crucial member of the pentose phosphate cycle, which produces and supplies NADPH for fatty acid synthesis. Unexpectedly, rubratoxin B decreased the activity of fatty acid synthase, which facilitates fatty acid chain elongation. However, because fatty acid synthase is not a key enzyme in fatty acid synthesis, its activity level in rubratoxin B-treated mice may be sufficient for lipid accumulation.
