Search for epigenome markers associated with an elevated risk of diabetes due to undernutrition in the fetal period

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K12727
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: University of Shizuoka
• Principal Investigator: Goda Toshinao 静岡県立大学, 食品栄養科学部, 教授 (70195923)
• Co-Investigator(Kenkyū-buntansha): 本間 一江 静岡県立大学, 食品栄養科学部, 助教 (80724765)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胎児期低栄養 / 糖尿病 / エピゲノム / バイオマーカー

Outline of Final Research Achievements

We have demonstrated that the undernutrition in the late fetal period in the rat leads to a reduced expression of ontogeny/differentiation-related genes in the pancreas, and a repressed expression of the genes coding transcription factors related to adipocyte differentiation in the adipose tissue, which should be respectively responsible for reduced insulin secretion and insulin sensitivity. In an animal strain predisposed to a reduced capability of insulin secretion, the undernutrition in the fetal period made worse the postprandial hyperglycemia in adulthood.
In search of the genes responding closely to postprandial hyperglycemia in the peripheral leukocytes of rats subjected to undernutrition in the fetal period, we have shown that inflammation-related genes, e.g., IL-1b, S100a8, S100a9 and S100a11, are putatively sensitive marker genes reflecting a postprandial hyperglycemic history

Free Research Field

保健栄養学、栄養生理学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的な意義は、胎児期の低栄養環境が、出生後の発達の過程で膵臓ならびに脂肪組織における分化や成熟化に関わる遺伝子の発現の低下をもたらすため、糖負荷による急激な血糖上昇が起こりやすく、糖尿病のリスクを高めることを示したことと、胎児期の低栄養環境による血糖上昇の履歴を示す候補遺伝子として炎症性サイトカイン遺伝子を同定したことである。
本研究は、遺伝素因の点で膵臓からのインスリン分泌能力の低い日本人にとって、妊娠時の栄養管理と胎児期における低栄養の予防が、糖尿病の発症・進展リスクの抑制のために、いかに重要かの根拠の一端を提示したものである。