A recent study sheds new light on why people gain weight from long-term stress and disruption to their circadian rhythms. It also helps to explain weight gain from the use of glucocorticoid drugs, which are often used in the treatment of rheumatoid arthritis and asthma. For the first time scientists think they have a molecular understanding of the reasons for the weight gain involved.

It's all to do with the peaks and troughs in the level of glucocorticoids in the body. Glucocorticoids are steroid hormones which include the stress hormone cortisol. The name is derived from the words glucose, cortex and steroid.

"It explains why treatments with glucocorticoid drugs, which are often essential for people with rheumatoid arthritis and asthma to even function, are so linked with obesity," says Mary Teruel, senior author of the study. "And it suggests ways in which such treatments can be given safely without the common side effects of weight gain and bone loss."

Usually, a healthy person's level of glucocorticoids should rise and fall over 24-hour cycle. There are the lowest at 3 am rising to a peak at 8 am to give a wake-up signal and get the appetite going. The cycle is governed by the body's circadian rhythm, a body clock that governs one's tiredness and wakefulness over the course of the day, and which can be affected by exposure to light.

Short spikes in glucocorticoid levels can also be caused by short-term stress or exercise, which is perfectly normal. However, long-term stress can lead to higher levels overall, as can the use of glucocorticoid drugs. This can affect how the body processes fat, but the research suggests this is all down to the timing of glucocorticoid pulses, which had never been studied before.

The team from Stanford University School of Medicine studied precursor fat cells in Petri dishes with varying exposures to glucocorticoids to see how they developed. They found the fat cell maturation increases if the ebb in glucocorticoids is shorter than 12 hours.

The researchers also experimented with glucocorticoids in mice. By feeding the mice glucocorticoid pellets, they were able to disrupt the natural glucocorticoid rhythms in the mice, leading to a doubling in fat mass. Mice fed pellets without glucocorticoid did not gain weight.

Further, mice injected with glucocorticoids did not gain weight if those injections coincided with normal peaks in glucocorticoid rhythm, even when glucocorticoid levels were increased 40 times.

Teruel thinks the research could help control weight gain in people. "Yes, the timing of your stress does matter," she explains. "Since conversion of precursor cells into fat cells occurs through a bistable switch, it means you can control the process with pulsing. Our results suggest that even if you get significantly stressed or treat your rheumatoid arthritis with glucocorticoids, you won't gain weight, as long as stress or glucocorticoid treatment happens only during the day. But if you experience chronic, continuous stress or take glucocorticoids at night, the resulting loss of normal circadian glucocorticoid oscillations will result in significant weight gain."

The team hopes that further research will shed light on the connection between glucocorticoids, food and insulin.

The study was published on April 3 in the journal Cell Metabolism.

Source: Stanford Medicine

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