Science: Obese mice treated with cytokines lose weight through "fat"

A research team led by the Perelman School of Medicine at the University of Pennsylvania has demonstrated how to treat obese mice with a cytokine called thymostromal lymphopoietin (TSLP), thereby significantly reducing abdominal fat and body weight
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The research team’s research found that, unexpectedly, the fat lost is not related to reducing food intake or speeding up metabolism.

"This is a completely unexpected discovery, but we have shown that fat reduction can be achieved by the skin secreting calories in the form of energy-rich sebum," said Taku Kambayashi, PhD, associate professor of pathology and laboratory medicine at the University of Pennsylvania and lead researcher.
Say
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She led the research with Dr.

The research team published a paper entitled " Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion " in the journal Science
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The author explains that obesity is a serious public health problem.
Globally, more than 40% of adults are overweight or obese
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Obese people have up to 7 times the risk of related chronic diseases, such as type 2 diabetes, fatty liver, heart disease and certain cancers

Kambayashi further explained: “Initially, we thought that TSLP had no effect on obesity itself
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” “What we want to know is whether it affects insulin resistance

To test the effect of TSLP on type 2 diabetes, the researchers injected a TSLP-expressing viral vector-adeno-associated virus 8 serotype (TSLP-aav) expressing TSLP-into obese mice on a high-fat diet (HFD)-which would increase TSLP levels in their bodies
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They found that after four weeks, TSLP carrier injection not only affected the diabetes risk in the treated mice, but actually reversed the animal's obesity

Most strikingly, obese mice treated with tslp decreased visceral fat, improved blood sugar and fasting insulin levels, and reduced the risk of fatty liver
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Visceral fat is white fat (or white adipose tissue; WAT), which is stored around the main organs of the abdomen and can increase the risk of diabetes, heart disease, and stroke

Given these dramatic results, Kambayashi hypothesized that TSLP effectively caused mice to get sick and reduce their appetite
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However, further tests showed that, compared with mice that were not treated with tslp, the mice treated with tslp actually ate 20?C30% more food than the control mice, and had similar energy expenditure and basal metabolism.

To explain the reason for the weight loss, Kambayashi recalled a small observation he had previously overlooked
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"When I looked at the fur of the tslp-treated mice, I noticed that they were shining in the light

Kambayashi thinks this is a far-fetched idea—is their greasy hair a sign that mice "sweat" fat from their skin? To test this theory, the researchers shaved the tslp-treated mice and the control mice , And then extract oil from their fur
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They found that Kambayashi's hypothesis was correct
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Glossy fur contains sebum-specific lipids
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Sebum is a high-calorie substance (highly specialized epithelial cells) produced by sebaceous cells in the sebaceous glands and helps to form the skin barrier
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The results of the study confirm that the oil released from the skin is the cause of the fat loss induced by tslp
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They commented: "Our findings support a model in which TSLP overexpression leads to WAT loss by inducing skin T cell migration and increasing sebum hypersecretion
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" "Therefore, we establish a paradigm in which fat loss can be Through the secretion of excessive sebum and revealing the role of adaptive immunity through the secretion of sebum, the skin barrier function.
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Our data provide a therapeutic concept that can lose calories through the secretion of fat and energy-rich form of sebum from the skin
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In order to study whether TSLP may play a role in controlling human oil secretion, the researchers then tested TSLP? 18 genes related to sebaceous glands in a public data set
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This reveals that TSLP? In healthy human skin, the expression of sebaceous gland genes is significantly positively correlated with the expression of sebaceous gland genes
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The authors of the study concluded that in humans, promoting sebum release can effectively lose weight by releasing fat through the skin
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They said: "Although body weight is unlikely to be controlled by sebum release in a homeostatic state, selective loss of WAT is feasible.
The release of sebum can be accelerated therapeutically, thereby passing "sweating fat" in the human body.
To achieve
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" Kambayashi's team plans to conduct further research to verify this hypothesis
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Kambayashi said: "I don't think we control weight naturally by regulating the secretion of sebum, but we may be able to hijack this process and increase the secretion of sebum, thereby achieving the goal of weight loss
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" "This may lead to the reversal of obesity and lipids.
New treatment interventions for disorders
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