Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring
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
Abstract
Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease.