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Techniques and Methods

Western diet since adolescence impairs brain functional hyperemia at adulthood in mice: rescue by a balanced ω-3:ω-6 polyunsaturated fatty acids ratio

International Journal of Obesity volume 49, pages 844–854 (2025)Cite this article

Subjects

Abstract

Background/Objective

Obesity is a devastating worldwide metabolic disease, with the highest prevalence in children and adolescents. Obesity impacts neuronal function but the fate of functional hyperemia, a vital mechanism making possible cerebral blood supply to active brain areas, is unknown in organisms fed a high-caloric Western Diet (WD) since adolescence.

Subjects/Methods

We mapped changes in cerebral blood volume (CBV) in the somatosensory cortex in response to whisker stimulation in adolescent, adult, and middle-aged mice fed a WD since adolescence. To this aim, we used non-invasive and high-resolution functional ultrasound imaging (fUS).

Results

We efficiently mimicked the metabolic syndrome of adolescents in young mice with early weight gain, dysfunctional glucose homeostasis, and insulinemia. Functional hyperemia is compromised as early as 3 weeks of WD and remains impaired after that in adolescent mice. These findings highlight the cerebrovascular vulnerability to WD during adolescence. In WD, ω-6:ω-3 polyunsaturated fatty acids (PUFAs) ratio is unbalanced towards proinflammatory ω-6. A balanced ω-6:ω-3 PUFAs ratio in WD achieved by docosahexaenoic acid supplementation efficiently restores glucose homeostasis and functional hyperemia in adults.

Conclusions

WD triggers a rapid impairment in cerebrovascular activity in adolescence, which is maintained at older ages, and can be rescued by a PUFA-based nutraceutical approach.

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Fig. 1: Glucose metabolism in mice fed a WD at adolescence is altered from 3 weeks to 10 months of diet compared to age-matched RD mice.
Fig. 2: Impaired functional hyperemia to whisker stimulations in adolescent, adult, and middle-aged mice fed a WD since adolescence compared to age-matched RD mice.
Fig. 3: Functional hyperemia dynamics during mouse development are different in mice under western diet versus regular diet.
Fig. 4: Impairment in glucose metabolism in mice with obesity due to WD is canceled by feeding with WD balanced in the ω-3:ω-6 PUFAs ratio.
Fig. 5: The amplitude of functional hyperemia is restored in adult WD-fed mice with a balanced ω-3:ω-6 PUFAs ratio.

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Data availability

All data generated or analysed during this study are included in this published article (and its Supplementary Information files). Detailed individual analysis will be made available upon request pending application and approval from the corresponding authors.

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Acknowledgements

We thank the animal core facility “Buffon” of the University of Paris Cité/Jacques Monod Institute for Animal Care.

Funding

HS had a postdoctoral fellowship award from NIH and AXA. MM had a doctoral fellowship award from Idex Université Paris Cité. This work was supported by the AXA Research Fund (MT).

Author information

Author notes

  1. Mireia Montaner

    Present address: Institute of Metabolic Science & MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, UK

  2. These authors contributed equally: Haleh Soleimanzad, Clémentine Morisset.

  3. These authors jointly supervised this work: Mickaël Tanter, Hirac Gurden.

Authors and Affiliations

  1. Physics for Medicine Paris, ESPCI Paris, INSERM, CNRS, PSL Research University, 75015, Paris, France

    Haleh Soleimanzad, Clémentine Morisset & Mickaël Tanter

  2. Université Paris Cité, Unit of Functional and Adaptive Biology (BFA), UMR 8251 CNRS, 75013, Paris, France

    Mireia Montaner, Christophe Magnan & Hirac Gurden

  3. Université Paris-Saclay, Institut d’Optique Graduate School, CNRS, Laboratoire Charles Fabry, 91127, Palaiseau, France

    Frédéric Pain

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Contributions

HS and CM equally contributed to the work. They designed the experiments, acquired and analyzed the imaging data along with MM for metabolic phenotyping. FP and CM edited the article. MT and HG equally contributed to the work. They designed the experiments and wrote the article together with HS, CM, MM, FP, and CM, MT and HG supervised the project.

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Correspondence to Mickaël Tanter or Hirac Gurden.

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All animal experiments were approved by the committee for animal care of Université Paris Cité and by the French Ministry of Research (agreement #17629) under the European directive 2010/63/UE.

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Soleimanzad, H., Morisset, C., Montaner, M. et al. Western diet since adolescence impairs brain functional hyperemia at adulthood in mice: rescue by a balanced ω-3:ω-6 polyunsaturated fatty acids ratio. Int J Obes 49, 844–854 (2025). https://doi.org/10.1038/s41366-025-01711-x

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