Weight Loss Seen In Mice By Boosting Cytokine And Making Them Sweat Fat

When it comes to weight loss, scientists have been engaging in many kinds of research. Their goal is to end obesity and improve health. While the perfect cure has yet to be discovered, these experts have also come a long way in terms of finding solutions.

Penn Medicine

Studies on mice have been conducted, and researchers have managed to induce weight loss in obese mice. They did this by boosting levels of an immune-signaling molecule called the “cytokine.” The mice did lose a lot of weight and fat loss did not come from eating less or having faster metabolism. Instead, they increased the secretion of the calorie-rich sebum from oil-producing glands in the animals’ skin.

Based on the findings made, the researchers created a proposal and said that immune-modifying drugs that induce the skin to “sweat” fat could be the very key to treat obesity to those who suffer from it.


Problems that Come with Obesity

It’s a fact that adults who are overweight or suffer from obesity are up to seven times as likely to develop chronic diseases, among which are type 2 diabetes, fatty liver disease, and heart disease. There is a significant increase of chances of contracting these diseases when compared to those who are in perfect shape or are considered to be within the moderate weight range.

In fact, several studies have been made regarding this matter, and according to the World Health Organization (WHO), more than 4 million people die each year because they happen to be overweight or obese. This is a reality that’s happening all over the world. Many individuals struggle to maintain a perfect weight. They either go through diet or exercise, or a combination of both. Yet, some find it hard to reach their goal. While there are few drug treatments available to help address the problem, many of these have side effects.


The New Treatment Strategy

Scientists may have come up with one novel treatment strategy. These are what the scientists have been exploring. Their goal is to target the body’s immune system because this has been known to affect the metabolism of fat or “adipose” tissue. This new focus has shown promising results, and future medicines for weight loss might target this exact need.

Researchers at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia had made speculations beforehand. They hypothesized that they could be able to treat insulin resistance in obese mice by boosting thee levels of a cytokine or immune signal called thymic stromal lymphopoietin (TSLP) in the rodent’s body.

Moreover, doctors have characterized type 2 diabetes by the body’s tissues no longer responding to insulin. And some of you may know, this is a hormone that regulates glucose levels in the blood. As the research progressed, the scientists were surprised to discover that TSLP not only improved glucose metabolism in the mice, but they also noticed how the mice lost weight in the process. Curiously enough, the weight loss that happened after was not associated with a faster metabolism, nor was it influenced by greater levels of physical activity, increased excretion of calories, or decreased intake of food. Rather, the mice with raised TSLP levels actually ate 20 to 30 percent more than the mice who were part of the control group.

Dr. Taku Kambayashi, Ph.D., was an associate professor of pathology and laboratory medicine at Penn. He led the study with medical student Ruth Choa, Ph.D. Together, they finally solved the puzzle and put together what they had found. The doctor said, “When I looked at the coats of the TSLP-treated mice, I noticed that they glistened in the light. I always knew which mice exactly had been treated, because they were so much shinier than the others.”

They also performed analysis on the hair from the treated mice. It showed that the animals were, in reality, secreting more fat-rich, calorie-dense sebum from the sebaceous glands on their skin. This then gave their fur a shiny, greasy appearance as an effect. Further details of the researchers’ report and findings are written in the scientific journal aptly named Science.


Weight Loss Happening on a High-Fat Diet

In order for the researchers to test the metabolic effects of TSLP, the scientists injected the obese mice with a virus that had been genetically engineered to carry the gene that makes cytokine, the important molecule that promoted weight loss. They then injected control mice with the same virus, but this time, without the additional gene.

After four weeks of observation, during which all the animals were made to eat a high fat diet, the control mice actually gained weight during the process. On the other hand, the mice injected with extra TSLP, the researchers noticed an improvement in the blood glucose and fasting insulin levels. Their weight also fell from an average of 45 grams (g) to a healthy 25 g.

The animals with cytokine in their system also lost visceral fat. This aforementioned fat is the white fat that accumulates around the vital organs. This could also be the very thing that happens to the humans who have gained weight. The experts have linked this to an increased risk of diabetes, heart disease, and of course, stroke. Because the mice started to sweat fat, the sebum produced had become evident on their skin, giving their fur a characteristically shiny appearance as a result.

The scientists wanted to confirm how the weight loss occurred as a result of increased sebum production. They did this by injecting the cytokine into obese mice that did not have the ability to produce sebum. As expected by the researchers, these mice had failed to lose any of the weight.

The cytokine that was injected seemed to work by sending immune cells to the skin. These cells then induced the sebum-producing sebaceous glands to produce unusually large amounts of the fatty substance. Sebum actually has a range of important functions, including blocking UV light, antimicrobial activity, and heat regulation.

Thus, the experiments revealed that, in addition to increasing and enhancing sebum production, the immune cells also increased the amount of antimicrobial proteins the cells had in them.


The Possible Immune Treatment to Address Obesity?

The researchers are optimistic about their discovery. They believe that the findings could inspire the creation of new drug treatments for overweight and obese people. What makes the treatments different this time around is that this work via the immune system by boosting the body’s ability for sebum production.

Prof. Kambayashi explained, “I don’t think we naturally control our weight by regulating sebum production, but we may be able to hijack the process and increase sebum production to cause fat loss. This could lead to novel therapeutic interventions that reverse obesity and lipid disorders.”

For the successive steps, the researchers plan to look further into how TSLP-activated T cells encourage sebaceous glands to increase sebum production. When it comes to humans, this may yield insights into skin diseases, such as eczema, in which the ability of the skin to act as a barrier fails and breaks down. Prof. Kambayashi spoke to Medical News Today about it and said, “It could also provide a potential therapeutic strategy for this disease.”

In humans, scientists say that there are two versions of TSLP: a short form and a long form. The latter is known to be the culprit behind inflammation and is known to exacerbate or cause asthma and other allergic diseases. Hence, the researchers hope to find the answer in the short form, the version that boosts sebum production. The dosage in a potential human treatment would also be likely much lower than the ones they used during the experiments they conducted with mice.

Prof. Kambayashi also talked to MNT and said, “In mice, TSLP-induced fat loss is dramatic (they will lose all their body fat in around 2 weeks).” He further stated, “In humans, I don’t think we need to increase sebum production to that extent. Rather, enhancing sebum production by threefold or so would be sufficient to get rid of calories from one extra burger per day.”

Because sebum results from the extraction of lipids from the bloodstream, he added, TSLP may improve cardiovascular health, in addition to inducing weight loss.


Formidable Challenges Faced for the Research

In an editorial that came with the paper, Marlon R. Schneider of the German Federal Institute for Risk Assessment in Berlin points to the “formidable challenges” that this new approach for weight loss faces. For one thing, there are major differences between the physiology of sebaceous glands in humans and in mice. There are also major differences in the composition of their sebum.

Additionally, the effects of producing this amount of sebum could very well be unpredictable. The fatty acids may block skin pores and may trigger acne. While there is no proof that this could happen, there is definitely a possibility.

“This is intriguing,” stated Naveed Sattar, Ph.D., professor of metabolic medicine from the University of Glasgow in the United Kingdom, who was not involved in the research. He explained to MNT, “But as the editorialist concludes, there are huge obstacles to thinking this new information would ever be useful to develop new treatments for obesity.” He further said, “My guess is ‘unlikely’ as the side effects on skin conditions […] may be limiting, even if this process works the same in humans, which requires confirmation.”

And while much has yet to be made and discovered, this could be a start. The research performed by the scientists and health experts could actually help open the doors for further research. Their findings could also be the very foundation of the cure that the humans need. This is certainly one area they need to look into because obesity has become such a rampant problem.

People all over the world do need help to lose weight and stay healthy. While diet and exercise does help, it’s not always easy for everyone. Many need that extra nudge to reach their goal weight, but it is also important to note that health comes first. We can only hope that the cure they come up with is not detrimental to the overall wellbeing of those who need it.