A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes

Low-carbohydrate ketogenic diets (LCKDs) are used for treating obesity and epilepsy; however, the molecular mechanism of LCKDs in tissues has not been fully investigated. In this study, novel LCKD-associated molecular targets were explored using gene expression profiling in the liver of mice fed a LCKD. The result showed that the LCKD promoted the expression of glycosyltransferase genes involved in ganglioside synthesis and suppressed the expression of Gm2a, the gene encoding GM2 ganglioside activator protein, a lysosomal protein indispensable for ganglioside degradation. These changes were correlated with increased ganglioside content in the liver and serum. As gangliosides are mainly expressed in central nervous tissues, we also analyzed LCKD effect on cerebral cortex. Although ganglioside levels were unchanged in mice on the LCKD, Gm2a expression was significantly down-regulated. Further analyses suggested that the LCKD altered the expression levels of gangliosides in a limited area of central nervous system tissues susceptible to Gm2a.