Sweat Away Fat to Fix Obesity

The University of Pennsylvania looking for a diabetes treatment have accidentally developed an innovative, even revolutionary treatment for weight loss. Treating obese mice with the cytokine known as TSLP led to significant abdominal fat and weight loss compared to controls.

Unexpectedly, the fat loss was not associated with decreased food intake or faster metabolism. TSLP stimulated the immune system to release lipids through the skin’s oil-producing sebaceous glands.

Above – Penn Medicine researchers discovered that obese mice were able to shed 40 percent of their body weight by secreting fat through their skin.

“This was a completely unforeseen finding, but we’ve demonstrated that fat loss can be achieved by secreting calories from the skin in the form of energy-rich sebum,” said principal investigator Taku Kambayashi, MD, PhD, an associate professor of Pathology and Laboratory Medicine at Penn, who led the study with fourth-year medical student Ruth Choa, PhD. “We believe that we are the first group to show a non-hormonal way to induce this process, highlighting an unexpected role for the body’s immune system.”

The animal model findings, Kambayashi said, support the possibility that increasing sebum production via the immune system could be a strategy for treating obesity in people.

The Hypothesis

Thymic stromal lymphopoietin (TSLP) is a cytokine — a type of immune system protein — involved in asthma and other allergic diseases. The Kambayashi research group has been investigating the expanded role of this cytokine to activate Type 2 immune cells and expand T regulatory cells. Since past studies have indicated that these cells can regulate energy metabolism, the researchers predicted that treating overweight mice with TSLP could stimulate an immune response, which could subsequently counteract some of the harmful effects of obesity.

“Initially, we did not think TSLP would have any effect on obesity itself. What we wanted to find out was whether it could impact insulin resistance,” Kambayashi said. “We thought that the cytokine could correct Type 2 diabetes, without actually causing the mice to lose any weight.”

The Experiment

To test the effect of TSLP on Type 2 diabetes, the researchers injected obese mice with a viral vector that would increase their bodies’ TSLP levels. After four weeks, the research team found that TSLP had not only affected their diabetes risk, but it had actually reversed the obesity in the mice, which were fed a high-fat diet. While the control group continued to gain weight, the weight of the TSLP-treated mice went from 45 grams down to a healthy 25 grams, on average, in just 28 days.

Most strikingly, the TSLP-treated mice also decreased their visceral fat mass. Visceral fat is the white fat that is stored in the abdomen around major organs, which can increase diabetes, heart disease, and stroke risk. These mice also experienced improved blood glucose and fasting insulin levels, as well as decreased risk of fatty liver disease.

Given the dramatic results, Kambayashi assumed that the TSLP was sickening the mice and reducing their appetites. However, after further testing, his group found that the TSLP-treated mice were actually eating 20 to 30 percent more, had similar energy expenditures, base metabolic rates, and activity levels, when compared to their non-treated counterparts.

The Findings

To explain the weight loss, Kambayashi recalled a small observation he had previously ignored: “When I looked at the coats of the TSLP-treated mice, I noticed that they glistened in the light. I always knew exactly which mice had been treated, because they were so much shinier than the others,” he said.

Kambayashi considered a far-fetched idea — was their greasy hair a sign that the mice were “sweating” out fat from their skin?

To test the theory, the researchers shaved the TSLP-treated mice and the controls and then extracted oils from their fur. They found that Kambayashi’s hypothesis was correct: The shiny fur contained sebum-specific lipids. Sebum is a calorically-dense substance produced by sebocytes (highly specialized epithelial cells) in the sebaceous glands and helps to form the skin barrier. This confirmed that the release of oil through the skin was responsible for the TSLP-induced fat loss.

The Conclusions

To examine whether TSLP could potentially play a role in the control of oil secretion in humans, the researchers then examined TSLP and a panel of 18 sebaceous gland-associated genes in a publicly-available dataset. This revealed that TSLP expression is significantly and positively correlated with sebaceous gland gene expression in healthy human skin.

The study authors write that, in humans, shifting sebum release into “high gear” could feasibly lead to the “sweating of fat” and weight loss. Kambayashi’s group plans further study to test this hypothesis.

We may be able to highjack the sebum process and increase sebum production to cause fat loss.

Journal Science – Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion

Sweat out the fat with TSLP!
Thymic stromal lymphopoietin (TSLP) is a cytokine that can promote immune responses that characterize allergic diseases. Choa et al. found that mice engineered to produce elevated TSLP displayed selective white adipose tissue loss that protected them from obesity, insulin resistance, and steatohepatitis (see the Perspective by Schneider). Protection was not mediated by eosinophils, regulatory T cells, or innate lymphoid cells. Rather, TLSP induced the migration of conventional T cells to sebaceous glands in the skin. Once there, these T cells promoted white adipose tissue loss by the hypersecretion of sebum, a lipid-rich substance that augments the skin’s barrier function. This mechanism, which likely evolved to enhance cutaneous antimicrobial defenses, could be possibly targeted in future treatments for obesity.

SOURCES – University of Pennsylvania, Science
Written by Brian Wang, Nextbigfuture.com

34 thoughts on “Sweat Away Fat to Fix Obesity”

  1. Sounds like a really effective, and really gross – way of losing weight. Can't see anyone wanting to go out in public covered with a greasy sheen and greasy hair.

  2. Thymic stromal lymphopoietin (TSLP) is a protein belonging to the cytokine family. It is known to play an important role in the maturation of T cell populations… Questions: would it lead to 'rapidly mutating T cell populations' of which there is a limited supply once the thymus-organ starts to peter out, which starts at ~age 30? If that is the case, misdirecting your T-cells for the purpose of aesthetics could put a life-long mortgage on your health. You might solve diabetes 2 and weight related conditions, but you'll become an easy target for infections… is the trade to look thinner and smell like bacon a good deal? I hope they can answer this question in a way that also regenerates my thymus in the process, so I'll have an unlimited supply of skinny, glistening health and black hair until I die by accident.

  3. Some good reading for the DIYers out there:

    A good article on the enhancement of transdermal drug delivery because we want to get that vitamin D down to the stratum basale. Getting vitamin D3 through the stratum corneum is not necessarily straight forward. TLDR of the linked study and a couple other studies out there, aloe vera gel +/- ethanol (among other things) are readily available absorption enhancers that should do the trick according to the best I can determine from available literature


  4. Very interesting. Here is a different article where they induced TSLP secretion in keratinocytes simply using topical vitamin D3 (available OTC).


    Downside is that a kind of atopic dermatitis was induced however the severity was not discussed. This sounds like a low-risk self experiment. Think I'll try it. Will reply to this post with results.

  5. It's Pyramid power! Food pyramid, that is.

    Well, I think that's part of it, but there is that evidence of lab animals gaining weight, too, on controlled diets. Hormone mimetics accumulating in the environment from birth control pills? An evolutionary advance in gut bacteria that spread across the world and across species?

  6. A cure for obesity would be good, but I'd also like to have someone figure out what is causing the dramatic increase in obesity since the mid 1950s. Otherwise, it seems likely that those cured of an episode of obesity would just develop it again.

    From what I have seen written about it over the years, nobody has really identified what has caused the large increase in the rate of obesity in the population. Attempts to pin it on poor diet or lack of exercise seem unable to account for more than a small fraction of the increase.

  7. Okay, but as a guy with really severe allergies who ALSO would like to drop 10 pounds… do I want my allergies getting that much worse?

  8. You know, that might actually be an interesting point to follow, relative acne to metabolic rate and caloric intake as an early adult.

  9. I don't think you have sebaceous glands in the intestinal lining. In this case, the more relevant risk would be oily skin and acne. But it also mentioned that this molecule was related to allergies. Maybe there would be inflammation or auto-immune side effects.

  10. Not as promising as Semaglutide. I really hope someone cures obesity soon. It does seem like researchers are finally closing in.

  11. Some sauna afterward might help to widen the pores enough that not a lot of pimples might form. As a person who has always had a rather oily skin, it's manageable.

  12. When I read these types of articles, I ask myself:

    Are there any potential bad side effects? After all, nothing is perfect. For each action, there seems to be a reaction.

    Of course, we take the good with the bad. Or we used to. Now it seems we have zero tolerance for risk.

    I am willing to accept risk if the returns justify it. There are side effects to a lot of medicines I take. But the upside (at least to me) justifies the risk of the side effects.

    But there are some risks I won't take, because the gains are not worth the gamble.

    So, if this new discovery could be used to help you lose weight without modifying diet and eliminates the need to exercise, but it meant you have uncontrollable loose, oily stools 4-5 times/week, would you go for it (so to speak)?….

  13. So in other words we're going to be a greased pig after taking it.

    And we thought high school pimples were bad…

Comments are closed.