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Peer-reviewedCC BY 4.0Nutrients

Maternal HFD and CDAHFD Exposure from Pregnancy to Lactation Differentially Affect Lipid Profiles and Behavior in Offspring Mice

5 affiliations
  1. 1Department of Functional Brain Activities, United Graduate School of Child Development, University of Osaka, Suita 565-0871, Osaka, Japan
  2. 2Center for Pharmaceutical Education, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Kanagawa, Japan
  3. 3Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji 910-1193, Fukui, Japan
  4. 4Laboratory of Pharmacotherapy, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Kanagawa, Japan
  5. 5General Health Medical Research Center, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Kanagawa, Japan

Abstract

Background/Objectives: Maternal nutritional status during pregnancy and lactation can influence metabolic and neurobehavioral development in offspring. However, the contribution of specific lipid alterations to these effects remains unclear. This study investigated whether maternal exposure to different high-fat diets produces distinct metabolic and neurobehavioral outcomes in offspring. Methods: Pregnant ICR mice were fed a control diet, a conventional high-fat diet (HFD), or a 50% choline-deficient, amino acid-defined high-fat diet (50% CDAHFD) from embryonic day 12 until weaning. Male offspring were assessed at 4–6 weeks of age for body weight, plasma lipid levels, behavioral phenotypes, prefrontal neurotransmitter release, and expression of genes related to serotonergic and dopaminergic signaling. A total of 31 dams and 196 offspring were used in the experiments and allocated to each experimental group. Results: Offspring in both HFD and 50% CDAHFD groups exhibited increased body weight and total cholesterol levels compared to controls, whereas plasma triglycerides were elevated a tendency in the 50% CDAHFD group. HFD offspring showed reduced spontaneous locomotor activity, and increased prefrontal serotonin release with altered serotonergic gene expression. Conversely, 50% CDAHFD offspring displayed increased exploratory behavior in the open field test alongside altered dopamine neuron-related genes, without locomotor or social deficits. Conclusions: Exposure of mothers to different high-fat diets has been suggested to cause specific changes in their offspring’s lipid profiles, which in turn modulate the serotonin and dopamine systems differently, leading to specific behavioral changes.

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BibTeX
@article{aoki2026maternal,
  title = {{Maternal HFD and CDAHFD Exposure from Pregnancy to Lactation Differentially Affect Lipid Profiles and Behavior in Offspring Mice}},
  author = {Ryoken Aoki and Nobuo Izumo and Megumi Furukawa and Rena Ikeda and Chisato Takiya and Ayaka Ito and Hideo Matsuzaki},
  journal = {Nutrients},
  year = {2026},
  month = oct,
  doi = {10.3390/nu18213589},
  url = {https://www.mdpi.com/2072-6643/18/21/3589},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Maternal HFD and CDAHFD Exposure from Pregnancy to Lactation Differentially Affect Lipid Profiles and Behavior in Offspring Mice
AU  - Ryoken Aoki
AU  - Nobuo Izumo
AU  - Megumi Furukawa
AU  - Rena Ikeda
AU  - Chisato Takiya
AU  - Ayaka Ito
AU  - Hideo Matsuzaki
PY  - 2026
DA  - 2026/10/29
JO  - Nutrients
DO  - 10.3390/nu18213589
UR  - https://www.mdpi.com/2072-6643/18/21/3589
AB  - Background/Objectives: Maternal nutritional status during pregnancy and lactation can influence metabolic and neurobehavioral development in offspring. However, the contribution of specific lipid alterations to these effects remains unclear. This study investigated whether maternal exposure to different high-fat diets produces distinct metabolic and neurobehavioral outcomes in offspring. Methods: Pregnant ICR mice were fed a control diet, a conventional high-fat diet (HFD), or a 50% choline-deficient, amino acid-defined high-fat diet (50% CDAHFD) from embryonic day 12 until weaning. Male offspring were assessed at 4–6 weeks of age for body weight, plasma lipid levels, behavioral phenotypes, prefrontal neurotransmitter release, and expression of genes related to serotonergic and dopaminergic signaling. A total of 31 dams and 196 offspring were used in the experiments and allocated to each experimental group. Results: Offspring in both HFD and 50% CDAHFD groups exhibited increased body weight and total cholesterol levels compared to controls, whereas plasma triglycerides were elevated a tendency in the 50% CDAHFD group. HFD offspring showed reduced spontaneous locomotor activity, and increased prefrontal serotonin release with altered serotonergic gene expression. Conversely, 50% CDAHFD offspring displayed increased exploratory behavior in the open field test alongside altered dopamine neuron-related genes, without locomotor or social deficits. Conclusions: Exposure of mothers to different high-fat diets has been suggested to cause specific changes in their offspring’s lipid profiles, which in turn modulate the serotonin and dopamine systems differently, leading to specific behavioral changes.
SN  - 2072-6643
ER  -