Shift work causes brain changes that increase appetite

Circadian misalignment changes the brain’s regulation of hormones, which could lead to shift workers to gaining weight, according to a new study.

Scientists from Bristol, UK, and the University of Occupational and Environmental Health in Japan say their findings reveal why night shift work is associated with changes in appetite.

For the study, published in Communications Biology, the team focused on glucocorticoid hormones in the adrenal gland, which regulate many physiological functions including metabolism and appetite.

Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some being orexigenic and others being anorexigenic.

Using animal models that comprised a control group and an out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated. This drove an increased desire to eat during the inactive phase of the day.

Rats in the control group ate 88.4% of their daily intake during their active phase and only 11.6% during their inactive phase.

In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase, equating to nearly five-times more (460% more) than what the control group consumed during the inactive phase.

The researchers say their findings show how disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues.

However, they suggest the neuropeptides identified may be promising targets for drug treatments adapted to treat eating disorders and obesity.

Study senior author Dr Becky Conway-Campbell, Research Fellow in Bristol Medical School: Translational Health Sciences (THS), said: “For people working throughout the night, a reversed body clock can play havoc with their health.

“For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours. However, internal brain messages to drive increased appetite are difficult to override with ‘discipline’ or ‘routine’ so we are currently designing studies to assess rescue strategies and pharmacological intervention drugs. We hope our findings also provide new insight into how chronic stress and sleep disruption leads to caloric overconsumption.”

Co-senior author Stafford Lightman, professor of medicine at Bristol Medical School, added: “The adrenal hormone corticosterone, which is normally secreted in a circadian manner, is a major factor in the daily control of brain peptides that regulate appetite.

“Furthermore, when we disturb the normal relationship of corticosterone with the day to night light cycle it results in abnormal gene regulation and appetite during the period of time that the animals normally sleep.

“Our study shows that when we disturb our normal bodily rhythms this in turn disrupts normal appetite regulation in a way that is at least in part a result of desynchrony between adrenal steroid hormone production and the timing of the light and dark cycle.”

Yoshimura M, Flynn B, Kershaw K et al. Phase-shifting the circadian glucocorticoid profile induces disordered feeding behaviour by dysregulating hypothalamic neuropeptide gene expression. Communications Biology 10 October 2023; doi: 10.1038/s42003-023-05347-3

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