Pre-fertilization-origin preservation of brown fat-mediated energy expenditure in humans
Environmental thermal stress substantially affects cellular plasticity of thermogenic adipocytes and energy balance through transcriptional and epigenetic mechanisms in rodents. However, roles of cold-adaptive epigenetic regulation of brown adipose tissue (BAT) in systemic energy metabolism in humans remained poorly understood. Here we report that individuals whose mothers conceived during cold seasons exhibit higher BAT activity, adaptive thermogenesis, increased daily total energy expenditure and lower body mass index and visceral fat accumulation. Structural equation modelling indicated that conception during the cold season protects against age-associated increase in body mass index through BAT activation in offspring. Meteorological analysis revealed that lower outdoor temperatures and greater fluctuations in daily temperatures during the fertilization period are key determinants of BAT activity. These findings suggest that BAT metabolic fate and susceptibility of metabolic diseases are preprogrammed by the epigenetic inheritance of cold exposure before the fertilization in humans.
Authors
- Hisashi Nakamura (ORCID: https://orcid.org/0000-0002-3158-370X)
- Yuko Kurosawa (ORCID: https://orcid.org/0000-0001-7321-6505)
- Makoto Arai (ORCID: https://orcid.org/0000-0003-3400-9815)
- Yu Wei (ORCID: https://orcid.org/0000-0001-8473-6856)
- Yoshihiro Matsumura (ORCID: https://orcid.org/0000-0002-3108-0440)
- Yoshiko Aoki (ORCID: https://orcid.org/0000-0002-7650-5254)
- Juro Sakai (ORCID: https://orcid.org/0000-0003-4043-1035)
- Yosuke Yamada (ORCID: https://orcid.org/0000-0001-7952-2706)
- Tsuyoshi Osawa (ORCID: https://orcid.org/0000-0002-9479-6665)
- Makoto Iida
- Takeshi Yoneshiro (ORCID: https://orcid.org/0000-0001-5298-5831)
- Tomoya Harada (ORCID: https://orcid.org/0000-0002-6820-4814)
- Miyuki Kuroiwa (ORCID: https://orcid.org/0000-0002-1403-1698)
- Sayuri Fuse-Hamaoka
- Toshimitsu Kameya
- Takafumi Hamaoka (ORCID: https://orcid.org/0000-0002-7470-5711)
- Masayuki Saito (ORCID: https://orcid.org/0000-0002-3058-3003)
- Ken-ichi Kuma
- Mami Matsushita
Institutions
- Toho University (JP)
- Tokyo Medical University (JP)
- Tohoku University (JP)
- Akita University (JP)
- Kyoto College of Medical Science (JP)
- Sapporo Science Center (JP)
- Institute for Renewable Energy (Poland) (PL)
- Tenshi College (JP)
- The University of Tokyo (JP)
- Kyoto University of Advanced Science (JP)
- Bukkyo University (JP)
- Hokkai Gakuen University (JP)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1038/s42255-025-01249-2
- Citations
- 13
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 15.14
Funders
- Japan Agency for Medical Research and Development
- Secom Science and Technology Foundation
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency