The gut-released peptide oxyntomodulin mediates the alignment of liver clock gene and metabolic transcript rhythms with the timing of food intake by postprandial induction of hepatic Per gene expression.
Humans and other animals have adapted their behavior and their biology to the daily cycle of light and dark. Groups of genes are reliably switched on or off at different times of the day and act as internal, or ‘circadian’, clocks that help these organisms to stay on a 24-hour cycle. External signals also synchronize the body’s internal clocks. For example, sunlight helps synchronize the master clock in the brain, while mealtimes and other cues help other organs keep time.
These internal clocks are often disrupted in people who work overnight or on rotating shifts. It is believed that when these individuals wake up or go to sleep at odd times it confuses their circadian clocks, which can be harmful to their health. People who work these unusual hours are at an increased risk of developing cancer, heart disease, obesity and other disorders that involve problems with metabolism.
Eating at odd hours may also throw off the circadian clocks in the digestive system. This may explain why metabolic problems have been linked to working odd hours. Landgraf, Tsang et al. hypothesized that if the hormones produced after eating are released when a person would normally be sleeping, this may desynchronize the circadian clock in organs like the liver. Screening mice and tissue samples from mice for hormones that perturb circadian rhythms showed that a hormone called oxyntomodulin, which is released from the gut after eating, activated important circadian clock genes in micemouse livers. The increases in clock gene activation were comparable to those seen in the brain in response to exposure to light.
Landgraf, Tsang et al. revealed that the clock-resetting effects of oxyntomodulin were the greatest when animals were exposed to it by eating, or by injections of the hormone, at times when the animals would normally be fasting. The experiments also showed that blocking oxyntomodulin prevented eating at unusual times from interfering with the liver’s circadian clocks. The findings may suggest a way to help protect people who work overnight from the harmful health effects linked to perturbed circadian clocks.
Oxyntomodulin regulates resetting of the liver circadian clock by food. Dominic Landgraf, Anthony H Tsang, Alexei Leliavski, Christiane E Koch, Johanna L Barclay, Daniel J Drucker, Henrik Oster. eLife 2015;10.7554/eLife.06253.