09 April 2018

Biorhythms and obesity

It was possible to explain the link between chronic stress and weight gain

Anna Kerman, XX2 century

In the course of a new study conducted at Stanford University, scientists for the first time managed to explain at the molecular level why people gain weight as a result of chronic stress, circadian (circadian) rhythm disorders and taking glucocorticoid medications. It's all about the daily fluctuations in the level of a group of hormones combined under the name "glucocorticoids" – first of all, the "stress hormone" cortisol. The results of the study are published in Cell Metabolism (Bahrami-Nejad et al., A Transcriptional Circuit Filters Oscillating Circadian Hormonal Inputs to Regulate Fat Cell Differentiation).

"The study suggests that weight gain can be slowed down by controlling the patterns of hormonal fluctuations," explains lead author Mary Teruel, associate professor of chemical and systems biology at Stanford.

This explains why treatment with glucocorticoid drugs (patients with rheumatoid arthritis, asthma and many other diseases often cannot do without these drugs) so closely related to obesity. Moreover, the study suggests ways to change therapy in such a way as to avoid common side effects: weight gain and bone loss.

Normally, 10% of the body's fat cells should die and be replaced by new ones. This proportion, the renewal of exactly one tenth of the lipocytes annually, allows us to maintain our current body weight. But, as the authors of the new study found out, if the decline in the level of glucocorticoids lasts less than 12 hours, the rate of maturation of lipocytes increases dramatically.

In a healthy person, the concentration of glucocorticoids in the blood fluctuates in accordance with the circadian rhythm. The indicator reaches a peak around 8 o'clock in the morning, and a minimum – about 3 o'clock in the morning. The rise in the level of glucocorticoids performs the function of a natural alarm clock: it indicates to the body the need to wake up and activates the feeling of hunger.

However, the level of these hormones in the blood depends not only on the time of day. Stressful situations increase the concentration of glucocorticoids, and short-term stresses (for example, exercise) – not for long, but chronic stress leads to a stable increase in the level of glucocorticoids.

Scientists have long known that these hormones trigger the mechanism of transformation of progenitor cells into fat cells. It has also been proven that adipose tissue contains a huge number of precursor cells ready to "grow" and take the "workplace" of lipocytes at a signal. However, normally less than 1% of immature adipose tissue cells reach maturity – this is necessary to replace damaged fat cells and maintain the body's fat depots in a healthy state.

Why do normal peaks of glucocorticoid concentrations (for example, daily or due to physical activity) not cause pathological maturation of lipocytes? And, on the other hand, why are disturbances in the rhythm of secretion of these hormones caused by chronic stress, jet lag or sleep disorders so closely associated with obesity?

After conducting a series of experiments, the authors of the study were able to demonstrate that the matter is in the frequency of ups and downs of the level of glucocorticoids. Cells in a culture that was exposed to hormones for 48 hours matured much more actively than in a culture in which hormones were fed at least at twelve–hour intervals - even though the total amount of glucocorticoids in different Petri dishes was the same.

The final stage of the study was an experiment on experimental mice. For 21 days, animals whose normal daily rhythm of glucocorticoid fluctuations was disrupted doubled their fat mass. Its growth was associated with both the appearance of new fat cells and an increase in the size of existing lipocytes. If the quadrupled doses of glucocorticoids were administered to animals in accordance with circadian rhythms, adipose tissue accumulation did not occur.

Offering a solution that would help control weight in people, Teruel says: "Yes, the moment of stress onset matters. Since the transformation of progenitor cells into lipocytes is controlled by a biological "switch", you can control this process by adjusting the hormonal "pulsation". Our results suggest that even against the background of serious stress or glucocorticoid therapy, it is possible not to gain weight – provided that both stress and the administration of drugs occur only during the day. But chronic continuous stress, as well as taking hormonal medications at night, disrupt normal fluctuations in the level of glucocorticoids, which leads to weight gain."

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