Researchers have found that desynchronizing the circadian rhythm in rats caused brain changes that had a significant impact on appetite and feeding behavior. The findings have important implications for night shift workers and those suffering jet lag and chronic sleep disturbances.
Our circadian rhythm – the biological body clock – regulates the production of glucocorticoids, hormones produced by the adrenal gland, which, in turn, moderate many physiological functions, including metabolism and appetite. Glucocorticoids are known to directly regulate brain peptides, or neuropeptides, that control appetite; some are orexigenic (increase appetite), while some are anorexigenic (decrease appetite). In humans, the main glucocorticoid is cortisol, which is considered the body’s ‘natural steroid'.
A new study led by researchers from the University of Bristol investigated how ‘circadian misalignment,' disruption of the body clock commonly associated with night shift or jet lag, affects the brain’s regulation of hunger-controlling hormones.
The researchers used rats with their adrenal glands removed and separated them into a control group and a ‘jet-lagged’ group. The control group received an infusion of corticosterone – the rat equivalent of cortisol – that mimicked the hormone’s release according to the light-dark cues seen in a normal day-to-night light cycle. The treatment group also received corticosterone, but it was shifted 12 hours out-of-phase with light-dark cues.
The researchers found that misalignment between the light-dark cues led to the dysregulation of one of the orexigenic neuropeptides, neuropeptide Y (NPY), in the out-of-phase rats, causing them to eat significantly more during the inactive phase of the day.
Rats in the control group ate 88.4% of their daily calorie intake during their active (that is, 'day') phase and only 11.6% during their inactive ('night') phase. In contrast, the ‘jet-lagged’ rats consumed 53.8% of their daily calories during their inactive phase without a corresponding increase in activity. This equated to the treatment rats consuming an incredible 460% more than the control group during the inactive phase.
The researchers also found that gene expression was significantly altered in the out-of-phase treatment group. They say their findings suggest that when daily glucocorticoid levels are out of sync with light and dark cues, appetite-affecting neuropeptides are significantly disordered.
“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,” said Stafford Lightman, a study co-author. “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.”
The researchers note that while there was no observable change in the rats’ body weight, probably due to the short five-day course of the study, the “remarkably robust changes” in feeding behavior were immediately evident and remained consistent throughout the experiment.
They say that the neuropeptides identified in their study may be promising future targets for drug treatments for eating disorders and obesity. And they offer some advice to those trying to override their nighttime appetite using only willpower.
“For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours,” said Becky Conway-Campbell, corresponding author of the study. “However, internal brain messages to drive the 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.”
The study was published in the journal Communications Biology.
Source: University of Bristol
