Short-term High Fructose Intake Reprograms the Transcriptional Clock Rhythm of the Murine Extraorbital Lacrimal Gland

Purpose: To determine whether high fructose intake (HFI) influences the daily transcriptional clock rhythms of murine extraorbital lacrimal glands (ELGs). Methods: Timed ELGs were collected from two groups of C57BL/6J mice subjected to a 12-hour light/12-hour dark (LD) cycle for 10 days; the first group received water-only feeding and the second received water with 15% fructose. Total RNA was extracted and subjected to RNA sequencing. A JTK_CYCLE algorithm and computational software were used to determine the periodicity, rhythmicity, and amplitude of the cycling transcripts. The rhythmic transcripts from different conditions were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: HFI feeding caused massive remodeling of the preexisting rhythmic genes in the normal control (NC)-fed ELGs. The induced transcripts in HFI-fed mice resulted in a profound reorganization of the coordinated transcriptional oscillations and KEGG pathways. Moreover, HFI feeding significantly altered the distribution of the KEGG pathways over an LD in the ELGs. Finally, we found that the ELGs have a robust core clock machinery and HFI feeding altered amplitude and the peak phase of clock gene transcriptional oscillation in ELGs. Conclusions: Short-term HFI reprograms the daily transcriptomic oscillation of murine ELGs. This information may deepen our understanding of the outcomes of lacrimal glands altered by nutritional challenge.