1:Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring
Science of the Month - April 2025
Na Yao, Kenichiro Kinouchi, Manami Katoh, Kousha Changizi Ashtiani, Sherif Abdelkarim, Hiroyuki Morimoto, Takuto Torimitsu, Takahide Kozuma, Akihide Iwahara, Shotaro Kosugi, Jin Komuro, Kyosuke Kato, Shun Tonomura, Toshifumi Nakamura, Arata Itoh, Shintaro Yamaguchi, Jun Yoshino, Junichiro Irie, Hisayuki Hashimoto, Shinsuke Yuasa, Akiko Satoh, Yohei Mikami, Shusaku Uchida, Takatoshi Ueki, Seitaro Nomura, Pierre Baldi, Kaori Hayashi, Hiroshi Itoh
Circadian rhythms are intrinsic, autonomous oscillations within an organism that occur on an approximately 24-hour cycle, synchronizing with environmental factors such as light and food. They are a homeostatic mechanism that allows the body to anticipate and adapt to diurnal changes. It was previously known that systemic factors derived from distant organs and individual behavior are important for the formation of organ rhythms, and that the circadian clock does not oscillate in pluripotent stem cells but is acquired during the differentiation process. In this study, we investigated the effects of maternal circadian rhythm in pregnant mice on fetal rhythms, organ development, and long-term postnatal metabolic prognosis. Maternal circadian rhythm disruption during pregnancy (CRD-P) led to a decrease in fetal and neonatal body weight, but organ differentiation and development were preserved. On the other hand, offspring born from CRD-P mothers exhibited hyperphagia, disrupted feeding rhythms, and increased leptin resistance when challenged with a high-fat diet, exacerbating obesity. Interestingly, CRD-P altered the phase relationship between maternal and fetal rhythms, leading to a compensatory increase in placental efficiency. The exacerbation of obesity in the offspring was not fully normalized by correcting the feeding rhythm alone but was normalized by intervening in both the feeding rhythm and food intake amount. This indicates that both hyperphagia and disrupted feeding rhythms contribute to the CRD-P-induced exacerbation of obesity. The Developmental Origins of Health and Disease (DOHaD) hypothesis, which posits that the environment during the fetal and neonatal periods affects future disease susceptibility, is well known. The results of this study suggest that the circadian rhythm as an intrauterine environment may be crucial for the long-term metabolic homeostasis of the next generation.
(Kenichiro Kinouchi, Department of Nephrology, Endocrinology and Metabolism, 85th Graduating Class)
Figure: Created with BioRender.com. Kinouchi, K. (2025)
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