Pre-fertilization-origin preservation of brown fat-mediated energy expenditure in humans

IF 18.9 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2025-04-07 DOI:10.1038/s42255-025-01249-2

Takeshi Yoneshiro, Mami Matsushita, Sayuri Fuse-Hamaoka, Miyuki Kuroiwa, Yuko Kurosawa, Yosuke Yamada, Makoto Arai, Yuchen Wei, Makoto Iida, Kenichi Kuma, Toshimitsu Kameya, Tomoya Harada, Yoshihiro Matsumura, Tsuyoshi Osawa, Yoshiko Aoki, Hisashi Nakamura, Takafumi Hamaoka, Juro Sakai, Masayuki Saito

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Abstract

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.

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人类棕色脂肪介导的能量消耗的受精前起源保存

环境热应激通过转录和表观遗传机制显著影响啮齿动物热源性脂肪细胞的可塑性和能量平衡。然而，棕色脂肪组织（BAT）的冷适应性表观遗传调控在人体全身能量代谢中的作用仍然知之甚少。在这里，我们报告了母亲在寒冷季节怀孕的个体表现出更高的BAT活性，适应性产热，每日总能量消耗增加，体重指数和内脏脂肪积累较低。结构方程模型表明，在寒冷季节受孕可以通过激活后代的BAT来防止与年龄相关的体重指数增加。气象分析表明，施肥期间较低的室外温度和较大的日温度波动是BAT活动的关键决定因素。这些发现表明，BAT的代谢命运和代谢性疾病的易感性是由人类受精前低温暴露的表观遗传预先编程的。

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.