In research led by Mary Teruel assistant professor of chemical and systems biology at Stanford University School of Medicine in California published 2018 year in the journal “Cell metabolism”the scientists discover the link between stress hormones and obesity.
Under stress the body produse hormones named clucocrticoids. During the day levels of these hormones rise and fall,a cicle regulated by our circadian rithm,they also used of our body to alleviate inflamation.
But when these hormones afect progenitor cells ( that is, the intermediate state between an undifferentiated stem cell and a fully differentiated one )they turn into fat cells and this leading to weight gain. A healthy person turns no more than 1 percent of their precursor or progenitor cells into fat cells, and does so when triggered by these hormones.
Teruel asked herself these questions :Why aren’t we drowning in fat every time glucocorticoid levels go high in the morning due to normal circadian rhythms or when our glucocorticoid levels spike when we exercise or go from a warm building out into the cold?And why is losing the normal rhythm of glucocorticoid secretion — such as in conditions of chronic stress,jet lag, and sleep disruption in shift-workers — so linked to obesity?”
To find out the answers scientists fulfill some experiments .In The first experiment they bath the progenitor cells with glucocorticoids in rithmic pulses for 4 days. They found that one 48-hour long pulse of the hormones caused most cells to turn into fat cells, whereas shorter pulses led to minimal cell differentiation.The scientists were answered themselves what makes the progenitor cells ignore short pulses but respond to longer ones.They used single-cell live imaging to track the activity of a protein that is known to correlate with the differentiation and maturity of a fat cell: PPAR-gamma (PPARG).
Tracking this protein in thousands of cells over the course of several days and using computer modeling revealed that there are two types of feedback that help the progenitor cells to ignore the normal circadian cycle of glucocorticoids and filter out only long hormonal pulses.
Authors of the experiment write, “this circadian filtering requires fast and slow positive feedback to PPARG.” Building on their previous research, the scientists also found other proteins that mediate a 34-hour feedback loop that enables PPARG to continue to accumulate, leading to more fat cells.
“Now we know the circadian code that controls the switch, and we’ve identified key molecules that are involved,” saysTeruel.
The scientists had to test if circadian code worked the same way in mammals. So, they increased glucocorticoid levels in a group of mice for 21 days and compared their weight with that of a control group of rodents.
The experiment revealed that the mices in the glucocorticoid-boosted group gained double the weight as the group of control mice. The scientists found, that this was due not only to the production of new fat cells, but also to the growth of already existing ones.
In the conclusion Teruel says:The findings, explain why treatments with glucocorticoid drugs, which are often essential for people with
Rheumatoid arthritis and asthma to even function, are so linked with obesity, and [suggest] ways in which such treatments can be given safely without the common sid e effects of weight gain and bone loss.”
“Yes, the timing of your stress does matter,” she says. “Since [the] 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 . “-continues Teruel- 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.”
She notes that the research illuminates the process of stress-induced weight gain in people, as well as offering clues for how to control it.