Researchers at Northwestern University and Evanston Northwestern Healthcare (ENH) have shown that a faulty or misaligned body clock, which regulates both sleep and hunger, can wreak havoc on the body and its metabolism, increasing the propensity for obesity and diabetes.
"The body clock is clearly controlling the elaborate brain signaling system that regulates appetite," says Joseph Bass, head of the division of endocrinology and metabolism at ENH.
They pose the theory that it may not only be how much one eats that contributes to obesity, but at what time, and how this affects the body.
As obesity gains hold on society, governments, scientists and the food industry are under growing pressure to tackle the issue.
The fight against obesity is gaining momentum in Europe, propelled by rising figures that show levels are far from leveling off.
Fresh figures released last month show in excess of 200 million adults across the EU may be overweight or obese.
And the number of European kids overweight is rising by a hefty 400,000 a year, according to the data from the International Obesity Task Force (IOFT).
The researchers demonstrated that an animal model with a known circadian disregulation - a mouse with a mutant 'clock' gene and therefore an imprecise body clock - had metabolic problems, including obesity and signs of the metabolic syndrome.
"This provides new genetic evidence that physiologic outputs of the biological clock, sleep and appetite are interconnected at the molecular and behavioral levels.
These yield implications on the role of internal biological timing in optimising strategies to reduce and sustain weight loss resulting from both medical and lifestyle modifications," said lead author Fred W. Turek.
Members of the research group involved in this latest study were involved in the team that cloned the first mammalian circadian gene, Clock, in 1997. This initial discovery provided the genetic model critical to the latest ENH study reported in Science.
For this latest study, scientists exposed mice to regular and high-fat diets and compared the response of the mutant animals to the response of the normal animals.
They discovered that the animals with the 'clock' mutation were unable to regulate their body weight in the presence of either diet.
The effect of the 'clock' mutation on body weight in animals fed a regular diet was similar in magnitude to the effect of a high-fat diet in normal mice.
When the 'clock' mutant animals were fed a high-fat diet, the combined effect of diet plus mutation led to the most severe alteration in body weight and changes in metabolism. The obese mice showed metabolic abnormalities in insulin secretion and the ability of the liver to handle sugar, report the researchers.
Obesity is associated with metabolic and cardiovascular disorders often referred to as the metabolic syndrome, which increases an individual's risk of developing a serious disease.
In addition to excess body weight, factors include high blood pressure, high insulin levels and one or more abnormal cholesterol levels: at the whole animal level, an inability to expend excess calories consumed.
Biological clocks function in the brain as well as lung, liver, heart and skeletal muscles. They operate on a 24-hour, circadian (Latin for 'about a day') cycle that governs functions like sleeping and waking, rest and activity, fluid balance, body temperature, cardiac output, oxygen consumption and endocrine gland secretion.
"The body clock regulates the time we go to bed, the time we get up and the time we get hungry - these are biological principles not psychological factors," said Bass. "This internal drive is a fundamental system that is important to health."
The findings are published in the 21 April 21 issue of Science.