iScience (Jul 2024)

Maternal high fat diet induces circadian clock-independent endocrine alterations impacting the metabolism of the offspring

  • Lu Ding,
  • Benjamin D. Weger,
  • Jieying Liu,
  • Liyuan Zhou,
  • Yenkai Lim,
  • Dongmei Wang,
  • Ziyan Xie,
  • Jing Liu,
  • Jing Ren,
  • Jia Zheng,
  • Qian Zhang,
  • Miao Yu,
  • Meltem Weger,
  • Mark Morrison,
  • Xinhua Xiao,
  • Frédéric Gachon

Journal volume & issue
Vol. 27, no. 7
p. 110343

Abstract

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Summary: Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.

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