Early life exposure to high fructose diet induces metabolic dysregulation associated with sex-specific cognitive impairment in adolescent rats.

The incidence of adolescent mental health disorders is on the rise. Epidemiological studies suggest that poor nutrition is a significant contributor to this public health crisis, specifically through exposure to high level of dietary sugar, including fructose, during critical periods of development. Previous studies have shown that elevated fructose exposure during adolescence disrupts mental health. Despite these data, it is currently unknown how fructose exposure, specifically during infancy, may impact adolescent mental health. We developed a rat experimental protocol to investigate the effects of fructose exposure during infancy on behavioral, cognitive and metabolic endpoints in adolescence. We found that exposing rats to high fructose from birth to weaning resulted in higher circulating glucose, insulin and leptin levels in adolescence. High fructose during infancy also increased bodyweight, disrupted metabolic homeostasis in the basolateral amygdala (BLA) as indicated by decreased activity of the cellular energy sensor AMPK, and impaired attention and impulsivity in a male-specific manner. This impaired attention observed in adolescent male rats following neonatal fructose exposure was partially rescued by viral-mediated, in vivo expression of a constitutively active form of AMPK in principal neurons of the BLA. Our results suggest that exposure to high level of fructose during infancy may impact adolescent mental health in a male-specific manner and that manipulation of AMPK activity may mitigate this impact.