Snacking may be gene-activated, suggests study
switching on of genes in brain that 'expect' food at irregular
hours, a result that has implications for obesity.
The new study, performed with mice, may go some way to explain dysfunctional eating patterns that play a role in human obesity, said the researchers from the University of Texas, particularly in the nocturnal eating often seen in obese people.
It may also have relevance to understanding "craving" in humans that has previously been linked to pleasure derived from the taste-aroma combination of foods in relation to both over-eating and obesity.
Over 300m adults are obese worldwide, according to latest statistics from the WHO and the International Obesity Task Force. About one-quarter of the US adult population is said to be obese, with rates in Western Europe on the rise although not yet at similar levels.
The UT researchers, led by Dr. Masashi Yanagisawa, trained mice to eat at a time when they normally wouldn't, and found that food turns on body-clock genes in a particular area of the brain. Even when the food stopped coming, the genes continued to activate at the expected mealtime.
The daily ups-and-downs of waking, eating and other bodily processes are known as circadian rhythms, which are regulated by many internal and external forces. One class of genes involved in these cycles is known as Period or Per genes.
When food is freely available, the strongest controlling force is light, which sets a body's sleep/wake cycle, among other functions, and is said to act on the so-called suprachiasmatic nucleus (SCN) area in the brain.
To start with, Dr. Yanagisawa and his team set the mice on a regular feeding schedule, and examined their brain tissue to find where Per genes were turned on in sync with feeding times.
The researchers then put the mice on a 12-hour light/dark cycle, and fed them for four hours in the middle of the light portion, going against the normal nightly feeding cycle of mice in order to model humans eating at inappropriate times.
Dr. Yanagisawa and his team report in the Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.0604189103) that the mice soon fell into a pattern of searching for food two hours before each feeding time. They also flipped their normal day/night behaviour, ignoring the natural cue that day is their usual time to sleep.
"This might be an entrance to the whole mysterious arena of how metabolic conditions in an animal can synchronize themselves with a body clock," said Yanagisawa.
Interestingly, it was found that after several days of this feeding routine the daily activation cycle of Per genes in the SCN was no longer affected, but other areas of the brain, most notably the so-called dorsomedial hypothamalic nucleus (DMH), the Per genes turned on strongly in sync with feeding time after seven days.
When food was withheld from the mice for two days, the scientists report that the genes continued to turn on in sync with the expected feeding time.
"They started to show the same pattern of anticipatory behaviours several hours before the previously scheduled time of feeding," said Yanagisawa.
"So somewhere in the body, they clearly remembered this time of day."
Better understanding of the multi-faceted problem of obesity could lead to more effective solutions for a condition that was recently described by the European Commissioner for Health and Consumer Protection as a threat to the physical and economical health of the EU and US.
Significant study is currently focussing on the role of diet in obesity. Indeed, one part of the €14.5m EU funding for the DIOGenes project is entitled, "Obesity, genes and diet at the population level," which will investigate the long-term role of dietary parameters in relation to other behavioural, environmental and genetic factors, in influencing obesity and its co-morbidities in the general population across Europe.
