Hypothalamic regulated physiological function and gene expression changes suggest high fructose corn syrup intake affects neurodevelopment in adolescent female rats.

Objective: To investigate the impact of drinking different caloric sweeteners from immaturity to young adulthood on hypothalamic controlled physiological functions and hypothalamic global gene expression using a rat model.

Methods: Young female Sprague-Dawley rats (age 28 days) were randomly assigned (n = 7 rats/group) to drink water sweetened with 13% (w/w) sugar as either high fructose corn syrup (HFCS), sucrose, fructose, or water (control) for 8 weeks. Hypothalamic controlled physiological function measurements included: energy intake, stress, and estrous cycles. RNA-sequencing (RNA-Seq) was used to investigate global differentially expressed genes (DEGs) in the hypothalamus.

Results: Rats drinking HFCS and sucrose solution increased liquid intake, but reduced food intake. Rats drinking HFCS had the highest (p < 0.05) absolute adrenal weight, which is indicative of chronic stress, and had lengthened estrous cycles. The DEGs with the highest fold changes in the hypothalamus of rats drinking HFCS compared to sucrose and fructose were involved in circadian sleep cycles, neuronal processes, and Engrailed-2 (En2) identified in autism spectrum disorder (ASD).

Conclusion: Among the different caloric-sweetened solutions, young female rats drinking HFCS solution showed food selectivity, elevated basal stress, and reproductive irregularity, which are characteristics associated with ASD. RNA-Seq revealed DEGs in rats drinking HFCS solution, included disrupted circadian sleep cycles, neurotoxicity, and ASD. The results of this preclinical study suggest that HFCS intake should be limited due to its potential for increasing the risk of neurodevelopmental disorders.