Unsaturated fat alters clock phosphorylation to align rhythms to the season in mice

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

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

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

A high-fat diet increased phosphorylation of the clock protein PERIOD2 (PER2) on serine 662 (S662).

Phosphorylation of PER2-S662 is necessary and sufficient for adjusting daily activity patterns to seasonal light cycles.
Increased PER2-S662 phosphorylation was associated with changes in gene expression pathways that convert polyunsaturated fatty acids into oxylipins in the hypothalamus.
Partial hydrogenation of dietary polyunsaturated fats led to increased PER2-S662 phosphorylation and adaptation to a summer light cycle in control mice.
Mice unable to phosphorylate PER2-S662 did not show the same adaptation to seasonal light cycles.

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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.