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Effects of Maternal High-Fat Diet During Pregnancy and Lactation on Behaviour and Hypothalamic Orexin Neurons in Mice

Takumi Katsuragi1, Takenori Tozawa1, Shunji Yamada2

  • 1Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience
|January 29, 2026
PubMed

Insights

Maternal high-fat diet (HFD) exposure during pregnancy and lactation increases offspring locomotion and orexin neuron activity in males, but these effects decrease with age. This suggests a temporary enhancement of activity in juvenile males due to HFD-induced changes in the lateral hypothalamus.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Nutritional Science

Background:

  • Maternal obesity is a known risk factor for offspring neurodevelopmental disorders.
  • Maternal diet during pregnancy and lactation may significantly impact offspring behavior and neurodevelopment.
  • The study investigates the specific effects of a high-fat diet (HFD) on offspring neurodevelopment.

Purpose of the Study:

  • To evaluate the impact of maternal HFD exposure during pregnancy and lactation on offspring locomotion.
  • To assess the effects of maternal HFD on orexin neuronal activity in the lateral hypothalamus (LH) of offspring.
  • To determine if these effects differ between male and female offspring and change with age.

Main Methods:

  • Dams were fed either a high-fat diet (HFD) or a control diet (CD) during gestation and lactation.
  • Offspring behavior was assessed using the open field test (OFT) and elevated plus maze (EPM).
  • Orexin A-positive neurons and c-Fos co-localization in the lateral hypothalamus were quantified using immunohistochemistry.

Main Results:

  • Male offspring exposed to maternal HFD showed increased locomotion and higher orexin A neuron counts in the LH.
  • These behavioral and neuronal changes were not observed in female offspring.
  • Locomotor activity in male offspring increased with age up to 13 weeks but normalized by 25 weeks, indicating a transient effect.

Conclusions:

  • Maternal HFD during pregnancy and lactation enhances locomotor activity and orexin neuronal activity in male offspring, particularly during juvenile stages.
  • The observed effects on locomotion and orexin neuron activity diminish with age.
  • Maternal HFD can transiently alter offspring neurodevelopment, specifically impacting locomotor behavior via orexin pathways in males.
Abstract

Keywords:
locomotion activitymaternal high‐fat dietneurodevelopmental disordersorexin neuron

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