1.リズム障害妊娠マウスから生まれた児の代謝予後に関する検討
夜間シフト業務を模倣する負荷をかけた妊娠マウスを用いて検討を行った。8〜24週齢の妊娠マウスを12時間明暗周期の環境下(コントロール群)、および慢性明暗周期変化(Chronic phase shifting: CPS群、5日に1回明暗周期を8時間前進)で飼育し、コントロール群およびCPS群の妊娠マウスより産まれたマウスを12時間の明暗サイクルの下で、低脂肪食負荷を3ヶ月間行い飼育すると共に、体重を継時的に計測したが、有意な差は見られなかった。また、代謝ケージを使用して、摂食、酸素消費、エネルギー消費などを計測するとともに、糖負荷試験やインスリン負荷試験を行い、耐糖能・インスリン抵抗性の評価を行ったが、コントロール群およびCPS群の間に有意な差は見られなかった。
母体内概日リズム障害による仔の長期概日代謝予後を検討するため、5ヶ月齢において日内の4つのタイムポイント (ZT 0, 6, 12, 18)において、肝臓、骨格筋、並びに血清を採取した。今後、肝臓の概日遺伝子発現を、トランスクリプトーム、メタボロームを利用して網羅的に検討を行うほか、MeDIP-seqなどで肝臓のエピゲノム変容の評価を行い、母体内概日リズム障害に起因する仔の概日代謝リプログラミングをクロマチンレベルで解析する。
2.低出生体重(Low Birth Weight: LBW)の長期予後に関する検討
LBWと軽度の腎機能障害との関係を明らかにした調査対象となった一貫教育校生徒の中から、その後の血圧と採血データのある対象の割り出しを行っている。
1. Examination of metabolic prognosis of infants born from rhythm disorder pregnant mice.
We conducted this study using pregnant mice with a load that mimics night shift work. Pregnant mice aged 8 to 24 weeks were bred in a 12-hour light-dark cycle environment (control group) and in a chronic phase shifting (CPS group, once every 5 days, the light-dark cycle was advanced by 8 hours). Mice born from pregnant mice in the control group and the CPS group were bred with a low-fat diet load for 3 months under a 12-hour light-dark cycle, and their weights were measured over time, but no significant difference was observed. In addition, feeding, oxygen consumption, energy consumption, etc. were measured, and glucose tolerance test and insulin tolerance test were performed to evaluate glucose tolerance and insulin resistance using metabolic gages. No significant difference was found between these groups. Liver, skeletal muscle, and serum were collected at 4 diurnal time points (ZT 0, 6, 12, 18) at 5 months of age to examine the long-term circadian metabolic prognosis of offspring due to maternal circadian rhythm disorders. In the future, we will comprehensively investigate the expression of circadian genes in the liver using transcriptome and metabolome. We will also evaluate the epigenome transformation of the liver using MeDIP-seq, etc., and analyze the circadian metabolic reprogramming of offspring at chromatin levels which is caused by maternal circadian rhythm disorder.
2. Examination of long-term prognosis of LBW
Among the students of the integrated education school who were the subjects of the survey that clarified the relationship between LBW and mild renal dysfunction, we are identifying the subjects who have subsequent blood pressure and blood sampling data.
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