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

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.