The clock of life ticks for metabolic health and disease
4 July 2006
Medical Research Council scientists have found a major clue to why shift workers suffer from increased incidence of heart disease and metabolic illnesses. The research published by a team at the MRC Laboratory of Molecular Biology in Cambridge, UK in the journal Current Biology (published) found that the daily "body clock" determines which enzymes are produced by the liver at which time of day and night. As a result, the ability of the liver to process meals and to deal with potentially toxic metabolites follows a regular daily progression.
When this progression is disrupted, as in mice with genetic disorders of the body clock, or in people subject to shift work, jet-lag, sleep disorders and simple old age these metabolic cycles will be compromised leading to serious long-term illness.
Dr Michael Hastings, who led the research, explained: "Circadian rhythms or 'body clocks' adapt us to the solar and social 24 hour world by driving our daily rhythms of behaviour, physiology and metabolism. When these natural cycles go awry we perform less well and feel dreadful. In particular, when our body clocks are disturbed so as to cause a mismatch between when and what we eat and what the body is able to process at meal times, nutrients are handled less effectively, for example fats will not be cleared from the blood stream and blood sugar levels will not be regulated appropriately."
Proteomics is the science of proteins and how they work. The new research used state of the art proteomic analysis to examine clock-controlled changes in the livers of normal mice and mice with genetically impaired body clocks.
Dr Hastings went on: "We discovered that around one fifth of liver enzymes show circadian rhythms, which means that the metabolic capabilities of the liver changes dramatically between day and night as different groups of proteins and enzymes are turned on and off in sequence. This is brought about by a new level of chemical co-ordination that we were never aware of, involving sophisticated modifications of proteins and their time-dependent synthesis.
Dr Hastings added: "Body clocks regulate the enzymes that control our vital liver functions such as nitrogen and sugar metabolism. Our research reveals a key mechanistic link between clock disturbance and the observed poorer health of long-term shift workers'
Dr Hastings and his team will be showcasing their research at this year's Royal Society's Summer Science Exhibition in London, 3-6 July.
