High-fat diet breaks the body clock in rats

When rats are fed a high-fat diet, this disturbs the body clock in their brain that normally controls satiety, leading to overeating and obesity. That’s according to new research published in The Journal of Physiology, which may be a cornerstone for future clinical studies that could restore the proper functioning of the body clock to avoid overeating.

Historically, it was believed that the master body clock was only located in a part of the brain called the hypothalamus. However, further research over the years has clarified that some control of our body’s daily rhythms (hormone levels, appetite, etc) lies in several other parts of the brain and body, including a group of neurons in the evolutionary ancient brainstem called the dorsal vagal complex (DVC).

The DVC has been shown to control food intake by inducing satiety. Research has also shown that in obesity, daily rhythms in food intake and the release of hormones related to eating are blunted or eliminated. However, it has not been clear if the malfunctioning of brain centres controlling appetite is a cause or the result of obesity.

Seeking an answer, researchers at Jagiellonian University and the University of Bristol studied two groups of rats: those fed a well-balanced control diet and those fed a high-fat diet. To mimic the impact of unhealthy diet on humans, the researchers introduced the new diet to adolescent rats (four weeks old) and monitored their food intake across 24 hours for four consecutive weeks.

Electrophysiological recordings were performed to measure how DVC neuronal activity changes across 24 hours. The use of multi-electrode arrays allowed for simultaneous monitoring of around 100 DVC neurons from each brainstem slice. This enabled the researchers to assess circadian changes of neuronal activity as well as neuronal responses to metabolically relevant hormones in each of the diet groups.

The researchers found that the rats fed high-fat diets, before they started to gain weight, showed changes in the DVC’s daily neuronal rhythms and the response of these neurons to appetite hormones. Thus, the researchers propose that disturbance in the DVC’s timekeeping leads to obesity, rather than being the result of excessive body weight.

While the human and mouse brainstem share common features, the major limitation of the study for its immediate translation to humans is that it was performed on nocturnal animals. The peak of the DVC activity was observed at the end of day, which is the rest phase for rodents but an active phase for people. Thus, it remains to be established if the phase of the brainstem clock is set to day and night, or whether it depends on patterns of rest and activity. Nevertheless, the study opens new research opportunities for trying to restore the body clock function of the DVC, and therefore tackling obesity.

“I’m really excited about this research because of the possibilities it opens up to tackle the growing health issue of obesity,” said first author Dr Lukasz Chrobok, from Jagiellonian University. “We still do not know what are the time cues which are able to reset or synchronise the brainstem clock. Hopefully, the restoration of daily rhythms in this satiety centre before or after the onset of obesity may provide new therapeutic opportunities.”

Image credit: ©stock.adobe.com/au/Grace800

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