Share on PinterestA fascinating study shows that by increasing the level of a certain cytokine, mice “sweat” fat. Carmen Jiménez / EyeEm / Getty Images
- Researchers have lost weight in obese mice by increasing levels of an immune signaling molecule, or “cytokine”.
- The fat breakdown did not result from a lower or faster metabolism, but from an increased secretion of high-calorie sebum from the oil-producing glands in the animals’ skin.
- The researchers suggest that immune-modifying drugs that stimulate the skin to “sweat” fat could be a strategy for treating obesity in humans.
Overweight or obese adults are up to seven times more likely to develop chronic diseases such as type 2 diabetes, fatty liver, and heart disease than those of moderate weight.
According to the World Health Organization (WHO), more than 4 million people die of overweight and obesity each year.
Many people have difficulty maintaining a moderate weight through diet and exercise alone. Although there are few drug treatments for overweight and obesity, they have side effects.
A novel treatment strategy that scientists are investigating is to fight 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 in Philadelphia speculated that they could treat insulin resistance in obese mice by increasing levels of a cytokine or immune signal called thymusstromal lymphopoietin (TSLP).
Doctors characterize type 2 diabetes by the fact that the body’s tissues stop responding to insulin, a hormone that regulates blood sugar levels.
The scientists surprisingly found that TSLP not only improved glucose metabolism in the mice, but also reduced their weight.
Oddly enough, the weight loss had no associations with faster metabolism, more physical activity, increased calorie excretion, or decreased food intake. In fact, the mice with elevated TSLP levels ate 20-30% more than the control mice.
DR. Taku Kambayashi, Ph.D.,an associate professor of pathology and laboratory medicine at Penn who co-led the study with medical student Ruth Choa, Ph.D., finally solved the puzzle.
“When I looked at the fur on the TSLP-treated mice, I noticed that they were shiny in the light. I always knew which mice were being treated because they were so much shinier than the others, ”he says.
Hair analysis of the treated mice showed that the animals secreted more high-fat, high-calorie sebum from the sebum glands of their skin. This gave their fur a shiny, greasy appearance.
The researchers report their results in Science.
To test the metabolic effects of TSLP, the scientists injected obese mice with a virus that had been genetically engineered to carry the gene that makes this cytokine.
They injected control mice with the same virus, minus the extra gene.
After 4 weeks of all animals on a high fat diet, the control mice gained weight. Meanwhile, mice supplemented with TSLP had improved blood sugar and fasting insulin levels, while their weight dropped from an average of 45 grams (g) to a healthy 25 g.
The 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 skin’s sebum production also increased, which gave the coat its characteristic, shiny appearance.
To confirm that the weight loss was as a result of increased sebum production, the researchers injected the cytokine into obese mice that lack the ability to produce sebum. As expected, these mice did not lose weight.
The cytokine appeared to work by sending immune cells to the skin, where they caused the sebum-producing sebum glands to produce abnormally large amounts of the fatty substance.
Sebum has a number of important functions, including blocking UV light, antimicrobial activity, and thermoregulating.
Experiments showed that the immune cells not only stimulated sebum production, but also increased the amount of antimicrobial proteins they contain.
The researchers are optimistic that their discovery could inspire new drugs for overweight and obesity that work through the immune system by boosting sebum production.
“I don’t think we can naturally control our weight by regulating sebum production, but we can possibly outsmart the process and increase sebum production to cause fat loss. This could lead to new therapeutic interventions that reverse obesity and fat metabolism, ”says Prof. Kambayashi.
Next, the researchers want to investigate how TSLP-activated T cells stimulate the sebum glands to increase sebum production.
In humans, knowledge can be gained from this about skin diseases such as eczema, in which the barrier function of the skin breaks down.
“It could also represent a potential therapeutic strategy for this disease,” Prof. Kambayashi told Medical News Today.
There are two versions of TSLP in humans: a short form and a long form. The long form is known to cause inflammation and to be implicated in asthma and other allergic diseases. The researchers therefore hope to find out that it is the short form that boosts sebum production.
The dosage in a possible treatment in humans would also be much lower than that used in their experiments with mice.
“In mice, TSLP-induced fat loss is dramatic (they will lose all of their body fat in about 2 weeks),” Prof. Kambayashi told MNT.
“I don’t think we need to increase sebum production in humans to this extent. Rather, a threefold increase in sebum production would be enough to eliminate calories from an extra burger per day, ”he said.
Since sebum results from the extraction of lipids from the bloodstream, he added, TSLP can improve cardiovascular health in addition to contributing to weight loss.
In an accompanying editorial, Marlon R. Schneider from the Federal Institute for Risk Assessment in Berlin points out the “huge challenges” for this weight loss approach.
For example, there are major differences between the physiology of the sebum glands in humans and mice and in the composition of their sebum.
In addition, the effects of large sebum production are unpredictable. The fatty acids can, for example, clog the skin pores and trigger acne.
“This is fascinating,” said Naveed Sattar, Ph.D., professor of metabolic medicine at the University of Glasgow in the UK, who was not involved in the research.
“But, as the editor-in-chief concludes, there are major barriers to assuming that this new information would ever be useful in developing new treatments for obesity,” he told MNT.
“My guess is ‘unlikely’ as the side effects are related to skin diseases […] can be limiting, even if this process works the same way in humans, which requires confirmation. “