2026-03-02 九州大学
（参考図）妊娠中に葉酸が不足すると、子どもの成熟後に肥満や異所性脂肪蓄積（脂肪肝、脂肪筋）が生じた。これには、肝臓や骨格筋におけるAmd1遺伝子の発現低下による脂肪酸の代謝効率低下が関与していた。
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1426
- https://www.kyushu-u.ac.jp/f/64974/26_0302_01.pdf
- https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(26)00080-X/fulltext
妊娠中の母親の葉酸値が低いと、男児の肝臓と筋肉における異所性脂肪蓄積が悪化する Low maternal folic acid during pregnancy exacerbates ectopic fat accumulation in the liver and muscle of male offspring
Tomoyo Kawakubo-Yasukochi ∙ Yoshikazu Hayashi ∙ Karen Tan ∙ … ∙ Eijiro Jimi ∙ Johan G. Eriksson ∙ Masato Hirata
Diabetes Research and Clinical Practice Published:February 14, 2026
DOI:https://doi.org/10.1016/j.diabres.2026.113161
Highlights
- In mice, low maternal FA disrupts hepatic one-carbon metabolism in adult male offspring, promoting metabolic dysfunction.
- In mice, low maternal FA induces obesity and ectopic fat accumulation in male offspring.
- In humans, maternal plasma FA levels are inversely associated with offspring ectopic fat, independent of FA supplementation.
Abstract
Background
Folic acid (FA), an essential nutrient for one-carbon metabolism, has been implicated in metabolic disease development. Although FA supplementation during pregnancy prevents neural tube defects, its broader metabolic effects remain unclear.
Methods
Eight-week-old C57BL/6 female mice were mated and fed an FA-deficient or control diet during gestation. Male offspring were weaned onto either a normal or Western-type diet, and monitored until 3 months of age. In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort, associations between maternal plasma FA levels during pregnancy and ectopic fat accumulation in offspring at age 6 years were examined.
Results
Maternal FA deficiency promoted ectopic fat accumulation in the liver and skeletal muscle of male offspring and increased obesity susceptibility. These effects were associated with disrupted one-carbon metabolism and impaired fatty acid β-oxidation, potentially due to reduced expression of Adenosylmethionine Decarboxylase 1 (Amd1) in male offspring. Consistently, in the GUSTO cohort, maternal plasma FA concentrations were inversely associated with hepatic and muscular fat accumulation in children.
Conclusion
Maternal FA status plays a critical role in regulating male offspring metabolic health. Maintaining adequate maternal plasma FA levels, rather than focusing solely on dietary intake, may be essential for preventing ectopic fat accumulation in the next generation.
