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Peer-reviewedCC BY 4.0Nutrients

Disentangling Fat and Sugar in the Western Diet: Parental Consumption of a High-Fat Diet Alters Offspring Brain Development

  • Gail Lee1,2
  • Karina Wilk3
  • Taylor DeYoung1,2,4
  • Cheryl Chong5
  • Emma G. W. McKnight1,2,4
  • Tiffany Ayoub1,2,4
  • Lloyd Fan6
  • Jacob Ellegood4,7
  • Antoine Beauchamp7
  • Jane A. Foster8,9
  • Tie-Yuan Zhang10
  • Jason P. Lerch1,3,11
2 more authors
  • Mark R. Palmert12,13,14
  • Brian J. Nieman1,2,4,15
15 affiliations
  1. 1Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5T 3H7, Canada
  2. 2Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
  3. 3Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
  4. 4Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
  5. 5Department of Biochemistry, University of Waterloo, Waterloo, ON N2L 3G1, Canada
  6. 6Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
  7. 7Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada
  8. 8Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8S 4L8, Canada
  9. 9Center for Depression Research and Clinical Care, Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75247, USA
  10. 10Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC H4H 1R3, Canada
  11. 11Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford OX3 9DU, UK
  12. 12Department of Physiology, The University of Toronto, Toronto, ON M5S 1A8, Canada
  13. 13Division of Endocrinology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
  14. 14Division of Endocrinology, BC Children’s Hospital, Vancouver, BC V6H 3N1, Canada
  15. 15Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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Abstract

Background: Maternal consumption of the Western diet is a precursor for metabolic conditions such as obesity and is associated with increased offspring risk for neurodevelopmental disorders (NDDs). It is not clear which component (i.e., high-fat or high-sugar) of the Western diet contributes to changes in offspring neurodevelopment. We used a mouse model of parental consumption of five different diets containing varying levels of fat and sugar to examine and compare their effects on offspring brain structure. Methods: Male and female offspring (avg n = 15/sex/diet) were assessed for differences in body weight and developmental milestone achievement, and their brains were imaged at postnatal day (P) 65 using magnetic resonance imaging to compare brain structure. Results: Offspring of the high-fat-only and combined high-fat/high-sugar diet groups showed delayed righting reflex success and heavier weight at weaning. Brain structure differences were also observed in early adulthood (P65), with the pattern of change induced by high-fat/high-sugar diets similar to that observed in some autism mouse models. Conclusions: Parental high-fat-only and combined high-fat/high-sugar diets altered offspring brain structure, but the high-sugar-only diet did not. High fat consumption is likely a key driver of the observed offspring brain changes and is a modifiable risk factor for NDDs.

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Cite

BibTeXRIS
BibTeX
@article{lee2026disentangling,
  title = {{Disentangling Fat and Sugar in the Western Diet: Parental Consumption of a High-Fat Diet Alters Offspring Brain Development}},
  author = {Gail Lee and Karina Wilk and Taylor DeYoung and Cheryl Chong and Emma G. W. McKnight and Tiffany Ayoub and Lloyd Fan and Jacob Ellegood and Antoine Beauchamp and Jane A. Foster and Tie-Yuan Zhang and Jason P. Lerch and Mark R. Palmert and Brian J. Nieman},
  journal = {Nutrients},
  year = {2026},
  month = oct,
  doi = {10.3390/nu18213539},
  url = {https://www.mdpi.com/2072-6643/18/21/3539},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Disentangling Fat and Sugar in the Western Diet: Parental Consumption of a High-Fat Diet Alters Offspring Brain Development
AU  - Gail Lee
AU  - Karina Wilk
AU  - Taylor DeYoung
AU  - Cheryl Chong
AU  - Emma G. W. McKnight
AU  - Tiffany Ayoub
AU  - Lloyd Fan
AU  - Jacob Ellegood
AU  - Antoine Beauchamp
AU  - Jane A. Foster
AU  - Tie-Yuan Zhang
AU  - Jason P. Lerch
AU  - Mark R. Palmert
AU  - Brian J. Nieman
PY  - 2026
DA  - 2026/10/27
JO  - Nutrients
DO  - 10.3390/nu18213539
UR  - https://www.mdpi.com/2072-6643/18/21/3539
AB  - Background: Maternal consumption of the Western diet is a precursor for metabolic conditions such as obesity and is associated with increased offspring risk for neurodevelopmental disorders (NDDs). It is not clear which component (i.e., high-fat or high-sugar) of the Western diet contributes to changes in offspring neurodevelopment. We used a mouse model of parental consumption of five different diets containing varying levels of fat and sugar to examine and compare their effects on offspring brain structure. Methods: Male and female offspring (avg n = 15/sex/diet) were assessed for differences in body weight and developmental milestone achievement, and their brains were imaged at postnatal day (P) 65 using magnetic resonance imaging to compare brain structure. Results: Offspring of the high-fat-only and combined high-fat/high-sugar diet groups showed delayed righting reflex success and heavier weight at weaning. Brain structure differences were also observed in early adulthood (P65), with the pattern of change induced by high-fat/high-sugar diets similar to that observed in some autism mouse models. Conclusions: Parental high-fat-only and combined high-fat/high-sugar diets altered offspring brain structure, but the high-sugar-only diet did not. High fat consumption is likely a key driver of the observed offspring brain changes and is a modifiable risk factor for NDDs.
SN  - 2072-6643
ER  -