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<p>During pregnancy mammals increase their food intake to accommodate the elevated metabolic demands associated with fetal growth and development. However, the molecular and neural circuit mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we demonstrate that arcuate nucleus agouti-related peptide (AgRP) neurons are activated and pro-opiomelanocortin (POMC) neurons are inhibited during pregnancy in mice. These changes are acutely required for promoting hyperphagia during pregnancy as chemogenetic inhibition of AgRP neurons or activation of POMC neurons both reduced the feeding of pregnant mice to non-pregnant levels. Finally, we utilized single cell resolution spatial transcriptomics in the arcuate nucleus of non-pregnant and pregnant mice to characterize pregnancy-induced changes in the transcriptomic state of arcuate nucleus neurons, including significant changes in many neurons controlling energy homeostasis, including AgRP and POMC neurons. Together, these findings outline a circuit mechanism regulating increased feeding during pregnancy, providing important mechanistic insights related to conditions at the intersection of reproduction and metabolism.</p>

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Reduced melanocortin tone modulates feeding during pregnancy in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Ingrid Camila Possa-Paranhos,
  • Kerem Catalbas,
  • Samuel Congdon,
  • Dajin Cho,
  • Tanya Pattnaik,
  • Christina Nelson,
  • Aarav Pathak,
  • Vraj Patel,
  • Patrick Sweeney

摘要

During pregnancy mammals increase their food intake to accommodate the elevated metabolic demands associated with fetal growth and development. However, the molecular and neural circuit mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we demonstrate that arcuate nucleus agouti-related peptide (AgRP) neurons are activated and pro-opiomelanocortin (POMC) neurons are inhibited during pregnancy in mice. These changes are acutely required for promoting hyperphagia during pregnancy as chemogenetic inhibition of AgRP neurons or activation of POMC neurons both reduced the feeding of pregnant mice to non-pregnant levels. Finally, we utilized single cell resolution spatial transcriptomics in the arcuate nucleus of non-pregnant and pregnant mice to characterize pregnancy-induced changes in the transcriptomic state of arcuate nucleus neurons, including significant changes in many neurons controlling energy homeostasis, including AgRP and POMC neurons. Together, these findings outline a circuit mechanism regulating increased feeding during pregnancy, providing important mechanistic insights related to conditions at the intersection of reproduction and metabolism.