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An intriguing study finds that increasing levels of a certain cytokine causes mice to “sweat” fat. Carmen Jimenez / EyeEm / Getty Images
  • Researchers have promoted weight loss in obese rats by increasing the levels of an immune signaling molecule or “cytokine”.
  • Fat loss did not come from eating less or faster metabolism, but from increased secretion of calorie-rich fat from the glands that produce oil in the skin of animals.
  • Researchers suggest that immune-modifying drugs that promote skin “sweating” fat may be a strategy for treating obesity in humans.

Adults overweight or obese are up to seven times more likely to develop chronic diseases, such as type 2 diabetes, fatty liver disease and heart disease, compared to moderately overweight individuals.

According to the World Health Organization (WHO), more than 4 million people die every year globally due to overweight and obesity.

Many individuals try to maintain a moderate weight only through diet and exercise. Although there are few medication treatments for overweight and obesity, they do have side effects.

A new treatment strategy that scientists are exploring is to target the immune system, which is known to affect the metabolism of fat or “adipose” tissue.

Researchers at the Perelman School of Medicine at the University of Pennsylvania at Philadelphia speculated that they could treat insulin resistance in obese rats by increasing levels of a cytokine or immune signal called thymic stromal lymphopoietin (TSLP).

Doctors characterize type 2 diabetes from body tissues that no longer respond to insulin, a hormone that regulates blood glucose levels.

The scientists were surprised to find that TSLP not only improved glucose metabolism in rats, but also lowered their weight.

Surprisingly, weight loss was not associated with a faster metabolism, higher levels of physical activity, increased calorie secretion, or decreased food intake. In fact, rats with elevated TSLP levels ate 20-30% more than control rats.

Dr. Taku Kambayashi, Ph.D.,an associate professor of pathology and laboratory medicine at Penn, who led the study with medical student Ruth Choa, Ph.D., finally solved the puzzle.

“When I looked at the coats of TSLP-treated mice, I noticed that they shone in the light. I always knew which mice were treated exactly because they were so much better than the others,” he says.

Hair analysis from treated rats showed that the animals were secreting higher-fat, high-calorie sebum from the sebaceous glands in their skin. This gave their wool a shiny, greasy look.

The researchers report their findings on sciencewith

To test the metabolic effects of TSLP, the scientists injected obese mice with a genetically generated virus to maintain the gene that makes this cytokine.

They injected control mice with the same virus, without the additional gene.

After 4 weeks, during which all animals ate a high-fat diet, control rats gained weight. Meanwhile, in rats with TSLP supplementation, fasting blood glucose and insulin levels improved, while their weight dropped from an average of 45 grams (g) to a healthy 25 g.

Animals lost visceral fat – the white fat that accumulates around vital organs – which experts have linked to an increased risk of diabetes, heart disease and stroke.

The production of fat also increased on their skin, giving their fur the characteristic shiny appearance.

To confirm that the weight loss occurred as a result of increased sebum production, the researchers injected cytokine into obese rats that do not have the ability to produce sebum. As predicted, these mice failed to lose weight.

Cytokines appear to work by sending immune cells to the skin, where they stimulate sebum-producing sebaceous glands to produce extremely large amounts of fatty substance.

Sebum has a number of important functions, including blocking UV light, antimicrobial activity, and heat regulation.

Experiments found that, in addition to increasing fat production, immune cells also increased the amount of antimicrobial proteins they contained.

Researchers are optimistic that their discovery could inspire new drug treatments for overweight and obesity that function through the immune system by increasing fat production.

“I do not think we naturally control our weight by regulating fat production, but we may be able to hijack the process and increase sebum production to cause fat loss. This could lead to new therapeutic interventions that reverse obesity. and lipid disorders, “says Prof. Kambayashi.

Next, researchers plan to investigate how TSLP-activated T cells encourage sebaceous glands to increase fat production.

In humans, this can provide insights into skin diseases, such as eczema, in which the skin’s ability to act as a barrier is disrupted.

“It can also provide a possible therapeutic strategy for this disease,” said Prof. Kambayashi for Medical News Todaywith

In humans, there are two versions of TSLP: a short form and a long form. The long form is known to cause inflammation and is involved in asthma and other allergic diseases, so researchers hope to discover that it is the short form that stimulates fat production.

The dose in a potential human treatment would also be much lower than that used in their experiments with mice.

“In rats, the fat loss caused by TSLP is dramatic (they will lose all of their body fat in about 2 weeks),” said Prof. Kambayashi MNTwith

“In humans, I do not think we should increase fat production to that extent. “On the contrary, increasing fat production by three times or more would be enough to get rid of calories from an extra hamburger a day,” he said.

Because sebum results from the removal of lipids from the bloodstream, he added, TSLP can improve cardiovascular health in addition to causing weight loss.

In an editorial accompanying the newspaper, Marlon R. Schneider from the German Federal Institute for Risk Assessment in Berlin points to the “frightening challenges” to this weight loss approach.

For example, there are major differences between the physiology of sebaceous glands in humans and rats, and in the composition of their fat.

In addition, the effects of producing large amounts of fat are unpredictable. Fatty acids can block skin pores and cause acne, for example.

“This is intriguing,” said Naveed Sattar, Ph.D., professor of metabolic medicine at the University of Glasgow in the UK, who was not involved in the search.

“But as the editorialist concludes, there are major obstacles to thinking that this new information would ever be useful to develop new treatments for obesity,” he told MNTwith

“My guess is ‘impossible’ as side effects on skin conditions […] it can be restrictive, even if this process works the same way in humans, which requires confirmation. “