Eight weeks of high-fat diet disrupted fasting/feeding rhythms in C57BL/6 mice, more severely in males than females. In males, the diet abolished circadian variation in glucose tolerance and glucose-stimulated insulin secretion, cut circadian-regulated islet transcripts by 42.1%, and reduced chromatin accessibility at insulin-secretion genes. Females kept normal circadian glucose control. Restricting food to the active (dark) phase restored glucose tolerance, insulin secretion and islet gene expression, and partly reversed shifts in D-box (DBP, TEF) and ETS transcription factor activity. Light-phase restriction did not restore rhythmicity.
The evidence comes entirely from mice, so it cannot be applied directly to people. Still, it supplies a mechanism for a pattern seen in human trials, where early time-restricted eating improves insulin sensitivity and beta-cell responsiveness in adults with prediabetes. The finding that eating in the wrong circadian phase actively suppresses islet rhythmicity fits human data linking night-shift work and late eating to higher type 2 diabetes risk. The sex difference is the most interesting result, and it hints that men may gain more from aligning meals with daytime, though that remains speculation until tested in humans. Mouse models of diet-induced obesity also exaggerate effects compared with typical human diets, and a rodent's dark phase maps imperfectly onto human waking hours. This is a preprint that has not been peer reviewed, so conclusions may shift. Overall it is a confirmatory, mechanistically rich advance rather than a paradigm shift, reinforcing the practical case for concentrating eating within daytime hours.