Disrupting body fat’s inbuilt clock may lead to weight gain

Scientists found that switching off the ‘clock’ gene (Arntl) in the fat cells of mice caused them to eat more food when they would normally be asleep, which led to them gaining more weight than normal mice, even when they did not consume more calories. The modified mice also showed changes in the production of hunger-signalling hormones and fat levels in the blood.

The findings may help to explain why shift-workers – whose day-night cycle is disrupted – are more likely to be obese, say the scientists from the Medical Research Council (MRC) who worked on the study in collaboration with researchers at the University of Pennsylvania in the US.

Dr Julian Griffin, Head of Lipid Profiling and Signalling at MRC Human Nutrition Research in Cambridge and an author of the study, said:

“This is the first demonstration that the clock gene Arntl in fat cells is important in regulating weight and that this is independent of the body’s ‘master clock’ in the brain. The next step will be to explore the role of the body clock in fat in human studies.

“We conducted the fat analysis at MRC Human Nutrition Research and discovered that in healthy mice polyunsaturated fat levels varied across the day, but this was disrupted when Arntl was prevented from working,” says Dr Griffin.

Altered mice also had increased levels of blood glucose, fat levels and insulin, which stayed high throughout the day and night. Their insulin levels – an important hormone involved in regulating fat and blood glucose levels – no longer varied between daytime and night-time as it should.

Previous research has shown shift workers and people with sleep disorders have a higher risk of developing obesity. The body clock, also called a circadian clock, is what allows our bodies to keep time and regulates our day-night cycle.

Dr Ann Prentice, Director of MRC Human Nutrition Research, said: “This research demonstrates the fascinating role fat plays in part regulating our body clock, and how this impacts on overall weight. In the future this work may have important implications for understanding why shift workers and others with altered day/night balances have an increased risk of developing obesity and type 2 diabetes.”

Notes to editors

The paper: ‘Obesity in mice with adipocyte-specific deletion of clock component Arntl’, by Paschos et al, is published in Nature Medicine.


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