2023 Fiscal Year Final Research Report
Studies on the effect of maternal uncarboxylated osteocalcin on the metabolic properties of next generation
| Project/Area Number |
20H03854
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
Hirata Masato 福岡歯科大学, 口腔歯学部, 客員教授 (60136471)
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| Co-Investigator(Kenkyū-buntansha) |
安河内 友世 (川久保友世) 九州大学, 歯学研究院, 准教授 (70507813)
溝上 顕子 九州大学, 歯学研究院, 准教授 (70722487)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 生活習慣病胎児期起源説 / オステオカルシン / グリコーゲンホスホリラーぜ / エピゲノム / one carbon metabolism |
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| Outline of Final Research Achievements |
An increasing amount of evidence indicates that an adverse perinatal environment contributes to a higher risk of metabolic disorders in later life of the offspring. We show that a maternal high-fat-high-sucrose diet during pregnancy causes metabolic disorders in the offspring via hypermethylation of the liver Pygl gene, encoding glycogen phosphorylase L, which mediates hepatic glycogenolysis. The lower expression of Pygl induced by the maternal diet causes the hepatic accumulation of glycogen and triglyceride in the offspring, which remains in adulthood. The administration of osteocalcin during pregnancy upregulates Pygl expression via both direct and indirect epigenomic pathways, resulting in the mitigation of the maternal diet-induced obesity and abnormal glucose and lipid metabolism in adulthood. We propose that maternal energy status is reflected in the hepatic glycogenolysis capacity of the offspring via epigenetic modification of Pygl and osteocalcin regulates glycogenolysis.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
生活習慣病、特に肥満に関わるDOHaD (Developmental Origin of Health and Disease; 生活習慣病胎児期起源説)の一例を分子メカニズムレベルで解明した学術的意義は大きい。また、妊娠期間中だけに投与したOCで、産仔の肥満を軽減する分子メカニズムも明らかにした意義も大きい。さらには母体に投与したOCが胎盤を介して胎児に、そしてさらに産仔に影響し肝臓内で自己再生的にOGが増える事を示した。今回の成果は、生活習慣病、特に肥満に対する新たな生理・薬理学的アプローチにつながる可能性がある。
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