Entrainment of the Circadian Clock in the Liver by Feeding

TLDR

Circadian rhythms of behavior are driven by brain oscillators coupled to light, while peripheral organs exhibit gene expression rhythms, yet the coordination of these rhythms into a coherent system remains unclear. The study examined how feeding cycles entrain liver, lung, and SCN gene expression rhythms using a luciferase‑reporter transgenic rat model. Restricted feeding entrained the liver rhythm by 10 hours within two days while the SCN remained light‑locked, demonstrating that the liver can be entrained independently of the SCN and light cycle. These results suggest that peripheral circadian oscillators such as the liver may be coupled to the SCN primarily through rhythmic behavior like feeding.

Abstract

Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated the effects of cycles of food availability (which exert powerful entraining effects on behavior) on the rhythms of gene expression in the liver, lung, and suprachiasmatic nucleus (SCN). We used a transgenic rat model whose tissues express luciferase in vitro. Although rhythmicity in the SCN remained phase-locked to the light-dark cycle, restricted feeding rapidly entrained the liver, shifting its rhythm by 10 hours within 2 days. Our results demonstrate that feeding cycles can entrain the liver independently of the SCN and the light cycle, and they suggest the need to reexamine the mammalian circadian hierarchy. They also raise the possibility that peripheral circadian oscillators like those in the liver may be coupled to the SCN primarily through rhythmic behavior, such as feeding.