We are regularly reminded that a balanced diet is key to staying healthy and preventing disease. What is less well known is that the time at which we eat may also be an essential to long-term health.
Central to this are circadian rhythms – commonly referred to as ‘body clocks’. These are endogenous daily rhythms that occur in every cell of the body; affecting a wide range of physiological processes, from when we sleep, to hormone levels, to how quickly we metabolise drugs. Our internal body clocks are synchronised with external day and night by the times when we eat and when we see light, and this is important for long-term health. Until recently, how our daily biological clocks sense and respond to feeding time was not understood.
Now work by John O’Neill’s group in the LMB’s Cell Biology Division and collaborators has identified insulin as the primary signal that communicates feeding time to synchronise circadian rhythms throughout the body. Their experiments show that insulin, a hormone released when we eat, resets circadian rhythms in many different cells and tissues, by stimulating production of a clock protein called PERIOD, an essential cog within every cell’s daily timekeeping machinery.
Working with David Bechtold at University of Manchester, the researchers found that the same thing happens in living mice, and that when mice are given a drug that temporarily blocks insulin signals, their body clocks become much less sensitive to meal times.
The researchers went on to show that if insulin is provided at the wrong biological time, when animals would normally be resting, it disrupts normal circadian rhythms: reducing their amplitude. This is directly analogous to shift work and jetlag, when body clocks are disrupted by abrupt changes in feeding and lighting schedule which, in the long-term, is strongly associated with increased risk of type 2 diabetes, cardiovascular disease and some cancers. The study suggests that paying particular attention to meal timing and light exposure can mitigate some of the adverse effects of shift-work, as well as helping to maintain healthy body clocks as we age.
This work was funded by the Medical Research Council, Dutch Cancer Foundation, AstraZeneca/LMB Blue Skies Initiative, and BBSRC.
Insulin/IGF-1 drives PERIOD synthesis to entrain circadian rhythms with feeding time. Crosby, P., Hamnett, R., Putker, M., Hoyle, NP., Reed, M., Karam, CJ., Maywood, ES., Stangherlin, A., Chesham, JE., Hayter, EA., Rosenbrier-Ribeiro, L., Newham, P., Clevers, H., Bechtold, DA., O’Neill, JS. Cell
John’s group page
David Bechtold’s page