Long-term high fructose intake reprograms the circadian transcriptome and disrupts homeostasis in mouse extra-orbital lacrimal glands

This study aims to explore the effects of long-term high fructose intake (LHFI) on the structure, functionality, and physiological homeostasis of mouse extra-orbital lacrimal glands (ELGs), a critical component of ocular health. Our findings reveal significant reprogramming of the circadian transcriptome in ELGs following LHFI, alongside the activation of specific inflammatory pathways, as well as metabolic and neural pathways. Notably, LHFI resulted in increased inflammatory infiltration, enhanced lipid deposition, and reduced nerve fiber density in ELGs compared to controls. Functional assessments indicated a marked reduction in lacrimal secretion following cholinergic stimulation in LHFI-treated mice, suggesting impaired gland function. Overall, our results suggest that LHFI disrupts lacrimal gland homeostasis, potentially leading to dry eye disease by altering its structure and secretory function. These insights underscore the profound impact of dietary choices on ocular health and highlight the need for strategies to mitigate these risks. •Prolonged high fructose intake disrupts the circadian rhythms in mouse lacrimal glands.•High fructose intake results in inflammation and structural alterations in lacrimal glands.•These changes lead to decreased lacrimal gland secretion, impairing its functionality.•The findings emphasize dietary adjustments to protect ocular health.