Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring.

Summary

In a mechanistic study, maternal circadian disruption during pregnancy programmed offspring toward obesity, with arrhythmic feeding, hypothalamic leptin resistance, and hepatic clock reprogramming. Aligning caloric restriction to the active phase in offspring nearly reversed the obese phenotype, highlighting a causal circadian programming of metabolic plasticity.

Key Findings

• Maternal circadian disruption reduced placental and neonatal weight yet preserved transcriptional and structural maturation.
• Offspring exhibited exacerbated diet-induced obesity with arrhythmic feeding, hypothalamic leptin resistance, and hepatic circadian reprogramming.
• In utero circadian desynchrony altered maternal–fetal phase relationships and placental efficiency.
• Temporal feeding restriction alone failed to prevent obesity, whereas circadian-aligned caloric restriction at the onset of the active phase nearly ameliorated the phenotype.

Clinical Implications

While preclinical, findings support counseling on circadian hygiene (stable sleep-wake cycles, light exposure, timed meals) during pregnancy and motivate trials of chrononutrition-aligned interventions to reduce offspring metabolic risk.

Limitations

• Preclinical murine model limits immediate clinical generalizability
• Duration- and sex-specific effects and human validation cohorts were not reported

Future Directions

Prospective human pregnancy cohorts to link maternal circadian metrics to offspring metabolic outcomes; interventional trials of circadian-aligned nutrition/light/sleep protocols during pregnancy; mechanistic dissection of placental clock pathways.