Investigation of the effect of low carbohydrate ketogenic diet on tissue expression of epilepsy-related glycosphingolipids

2019 Fiscal Year Final Research Report

• Project/Area Number: 15H02907
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Eating habits
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Okuda Tetsuya 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (20443179)
• Co-Investigator(Kenkyū-buntansha): 森田 直樹 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ付 (60371085)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: ケトン食 / ガングリオシド / てんかん / GM2A / ST3GAL2 / 脂肪肝 / VLDLR / レプチン

Outline of Final Research Achievements

Molecular targets associated with low-carbohydrate ketogenic diets (LCKDs) 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.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

てんかん患者の約３割は治療薬が奏効しないが、ケトン食はこのような難治性てんかんであっても改善できる。しかし、食べにくい、重度の便秘になるなど課題も多い。本研究によりケトン食の分子作用点が解明され、その作用を評価するための分子マーカーを開発できれば、その応用により患者に負担の少ないてんかん治療食の開発や創薬へとつながる点に社会的な意義がある。また、研究対象とするガングリオシドは様々な神経疾患の原因となるが、中枢神経組織における機能・役割は明確になっておらず、その解明につながる成果が期待できる点に学術的な意義がある。