Science (New York, N.Y.)Oct 23, 2025

Unsaturated fat changes clock protein activity to adjust daily rhythms for the season in mice

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Dietary unsaturated fat shifted seasonal circadian alignment in mice through phosphorylation of PER2 at S662.

Evidence

A mouse diet and photoperiod experiment measured locomotor phase shifting, hypothalamic expression pathways for PUFA-derived oxylipins, and PER2-S662 phosphorylation, including mice whose PER2-S662 could not be phosphorylated.

Caveat

The result is limited to mouse circadian entrainment and specific dietary manipulations, not direct evidence about human seasonal adaptation.

Simplified

The circadian clock maintains synchrony between biological processes and light/dark cycles by integrating environmental cues. How the clock adapts to seasonal variations in the environment is incompletely understood. We found that a high-fat diet increased phosphorylation of the clock protein PERIOD2 (PER2) on serine 662 (S662), which was necessary and sufficient for regulating phase shifting of daily locomotor activity to entrain to seasonal light cycles. PER2-S662 phosphorylation correlated with genome-wide expression pathways that regulate polyunsaturated fatty acid (PUFA) conversion into oxylipins in the hypothalamus. Partial hydrogenation of dietary PUFAs increased hypothalamic PER2-S662 phosphorylation and entrainment to a summer photoperiod in control mice, but not in mice for which PER2-S662 could not be phosphorylated. PER2-S662 phosphorylation is influenced by, and alters the regulation of, unsaturated fat to control circadian phase shifting across the seasons.