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

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. 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). 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. 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.