That is the first study to prove explicitly that insulin activity is controlled by the body's biological clock. The study published in the Current Biology, helps explain why not just what you eat, but when you eat, also matters.
"Our study confirms that it is not only what you eat and how much you eat that is important for a healthy lifestyle, but when you eat is also very important," said postdoctoral fellow Shu-qun Shi, who performed the experiment with research assistant Tasneem Ansari in the Vanderbilt University Medical Center's Mouse Metabolic Phenotyping Center.
The research was conducted by a team of Vanderbilt scientists directed by Professor of Biological Sciences Carl Johnson and Professors of Molecular Physiology and Biophysics Owen McGuinness and David Wasserman.
Because mice are nocturnal, they have a circadian rhythm that is the mirror image of that of humans: They are active during the night and sleep during the day. In all other respects, the internal timekeeping system of the two species work very similarly at the molecular level.
"People have suspected that our cells' response to insulin had a circadian cycle, but we are the first to have actually measured it," said McGuinness. "The master clock in the central nervous system drives the cycle and insulin response follows."
The research team found that normal "wild-type" mouse tissues are comparatively resistant to insulin during the inactive phase whereas they become more active on the insulin [better able to transfer glucose out of the blood] during the high activity phase of their 24-hour cycle. As a consequence, sugar is converted into fat during the inactive phase and consumed for producing energy during the high activity phase.
"That is why it is good to fast every day...not eat anything between dinner and breakfast," said Johnson.
The researchers also examined what happened to insulin action when the circadian clocks of individual mice got out of sync.
To put their clocks out of sync, normal mice were kept in a constantly lit environment. In this case, mice were locked in the inactive/fasting phase. As a result,despite actually eating less food, they developed a higher proportion of body fat and gained more weight on a high-fat diet than regular mice. Obesity and the insulin resistance that accompanies it, increases the risk of diabetes and cardiovascular disease.
This explains the increased occurrence of obesity and diabetes among night-shift workers and people suffering abnormal sleep patterns.
The study also showed that high-fat diets disturb the circadian clock. As a result, their insulin cycle defaulted to the inactive/fasting phase, which helps explain why high-fat diets lead to weight gain.
So sleeping on time, eating on time is critical for a keeping diabetes, heart disease and obesity at bay.
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