NEW YORK — Disrupting your circadian clock — which regulates your body rhythms over a 24-hour day — plays a critical role in gaining weight. Researchers from Weill Cornell Medicine conducted two studies that found stress at the wrong time of the day can alter a person’s metabolism, leading to more fat building up.
“A lot of forces are working against a healthy metabolism when we are out of circadian rhythm,” explains senior author Dr. Mary Teruel, associate professor of biochemistry and a member of the Gale and Ira Drukier Institute for Children’s Health, in a media release. “The more we understand, the more likely we will be able to do something about it.”
In the first study, published in Cell Reports, Dr. Teruel and her team replicated the effects chronic stress has on daily fluctuations in glucocorticoids, a class of stress-related hormones. They implanted pellets into mice which consistently released glucocorticoids over 21 days under the skin and then compared these animals with normal mice experiencing normal hormone fluctuations.
The amount of brown and white fat in the mice carrying the glucocorticoid implants doubled over the 21 days, with insulin levels skyrocketing even though the mice in both groups ate the same exact diet.
“If you stress the animals at the wrong time, it has a dramatic effect,” Dr. Teruel says. “The mice aren’t eating differently, but a big shift in metabolism causes weight gain.”
Interestingly, the team also found that metabolic disruptions have a “protective effect” which keep blood sugar levels low and prevent fat from building up in the blood and liver. When the team removed the pellets, this trend quickly changed.
“It shows the animals can cope with chronic stress for a while,” Teruel adds.
‘The decision to become a fat cell happens rapidly’
In the second study, published in the Proceedings of the National Academies of Sciences, study authors attached a red fluorescent protein to proteins which control the expression of circadian clock genes. They also attached a yellow fluorescent protein to peroxisome proliferator activated receptor gamma (PPARG), another protein which regulates the production of fat cells.
The fluorescent markers helped researchers monitor the daily changes in PPARG and circadian gene expression in each mouse’s fat cells. During the time of day the circadian clock is in its “rest period,” researchers found a circadian gene called CCAAT enhancer binding protein alpha (CEBPA) triggers a rapid increase in PPARG. Once PPARG production reaches a certain level, the precursor cells fully commit to becoming fat cells. This process takes a few days to complete.
“The decision to become a fat cell happens rapidly over 4 hours. It is like a switch,” Teruel reports. “It only happens at a certain time of day.”
Study authors are now working on figuring out why disruptions in our daily rhythms actually protect metabolism. They’re also looking to see if stress-related changes and high-fat diets make these changes permanent. Their findings may eventually lead to the creation of a drug that can reset the circadian rhythms in obese people.
“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” the study author concludes. “We are trying to understand how they work together and how we can coordinate them.”
