Researchers at UCSF discovered that a high-fat diet shifts the body's internal clock by increasing phosphorylation of a single site on the protein PER2 (serine 662). This molecular change slows the clock's ability to advance toward winter light cycles but speeds its adaptation to summer light cycles. Caloric restriction had the opposite effect. When the team used genetic mutations to block or mimic this phosphorylation, they replicated the dietary effects entirely. Further, polyunsaturated fatty acids in the diet appear to drive oxylipin production in the hypothalamus, which modulates this phosphorylation. The findings reveal a direct biochemical pathway linking seasonal food composition to circadian entrainment in mice.
