Researchers discovered an incredible side effect when they were attempting to improve the insulin sensitivity of obese mice using an immune protein called TSLP: the mice were literally sweating off weight.
Mice Sweat The Fat Out
A new study from the University of Pennsylvania School of Medicine has made obese mice literally sweat off excess fat weight. The mice were treated with a special cytokine, a protein produced by the body and used for signalling of various different kinds, which made them sweat off excess weight in the form of sebum, an oily secretion that lubricates the skin and hair. In time, treatment with these cytokines could be used to help obese people lose weight as well.
The study itself was actually supposed to be a study of how the cytokine – called TSLP – on insulin resistance, but the scientists soon discovered that it was having an amazing effect on the mice’s body composition.
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TSLP is involved in asthma and other allergic diseases, and the researchers had been investigating the broader role of this cytokine with regard to metabolism and weight. Studies had already indicated that these cells can regulate energy metabolism, and so 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,” 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 thought that the cytokine could correct Type 2 diabetes, without actually causing the mice to lose any weight.”
To test the effect of TSLP on Type 2 diabetes, the researchers injected obese mice with a viral vector to increase their TSLP levels. After four weeks, the research team found that TSLP had not only affected their diabetes risk, but also reversed the obesity in the mice, which were being 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 so-called “white” fat that is stored in the abdomen around major organs. Increased visceral fat mass 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.
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At first, the researchers believed the weight loss was due to the TSLP causing the mice to lose their appetites, but after further testing, they found that the TSLP-treated mice were actually eating 20 to 30 percent more, had similar energy expenditures, base metabolic rates, and activity levels, in comparison to their non-treated counterparts.
A minor observation proved key to understanding what was happening.
“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,” Kambayashi said.
Could the mice’s greasy hair be a sign that they were “sweating” out fat from their skin?
To answer the question, the researchers shaved the TSLP-treated mice and the controls and then extracted oils from their fur. They found that the shiny fur contained sebum-specific lipids. Sebum is a calorically-dense substance produced by sebocytes (highly specializedepithelial 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.
To examine whether TSLP could potentially play a role in the control of oil secretion in humans, the researchers then examined TSLP and a variety of genetic data, which together showed that TSLP expression is significantly and positively correlated with sebaceous gland gene expression in healthy human skin.
It is therefore entirely possible that humans could ‘sweat’ excess fat loss off by kicking sebum release into “high gear”. The researchers plan a further study to test this hypothesis.
“I don’t think we naturally control our weight by regulating sebum production, but we may be able to highjack the process and increase sebum production to cause fat loss. This could lead to novel therapeutic interventions that reverse obesity and lipid disorders,” Kambayashi said.
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