These Obese Mice Lost Weight By “Sweating” Their Fat, According To Penn’s Team | Way of life


PHILADELPHIA – In search of better treatments for type 2 diabetes and other consequences of obesity, Taku Kambayashi has long questioned whether he could harness a bodily function that most people think of in a very different: the immune system. There was some evidence to suggest that this approach might work, as certain types of immune cells were known to play a role in metabolism.

But when he and his colleagues at the University of Pennsylvania stimulated these cells in a series of experiments on obese mice, they were surprised. Not only did the animals become healthier in terms of blood sugar levels and other metabolic “markers”, they also lost considerable amounts of weight.

Within four weeks of triggering the animals’ immune response, Kambayashi and graduate student Ruth Choa found that the mice had lost 40% of their body weight, on average. It was all in the form of fat.

Additionally, careful measurements revealed that the animals’ weight loss was not the result of faster calorie burning or less food consumption. In fact, they were eating even more than before. The real answer, scientists reported in Science Thursday after many months of detective work, was that mice were “sweating” fat molecules through their skin.

“It’s wild,” said Kambayashi, associate professor of pathology and laboratory medicine at Penn’s Perelman School of Medicine.

The billion dollar question is, of course, whether this phenomenon could be exploited in humans. At the moment, the answer is not clear and all the usual caveats apply. Mice are not humans. All manner of remedies for cancer and other ailments have shown promise in laboratory animals, only to go away when tried in humans.

Yet humans are known to secrete fatty molecules through the skin, just like mice, but at low levels. The oily substance is called sebum, produced by the sebaceous glands and found on the skin and hair. (It’s distinct from sweat; Kambayashi used this term in his article just to get the idea across to the general public.)

The average person secretes 130 calories from sebum per day, which is not enough to impact body weight. But if this process could be speeded up, say, quadruple, Kambayashi thinks he would be on to something.

“You would lose a pound of fat per week,” he said.

Others in the field are taking a wait-and-see stance because obesity is a complex disorder. Among them is Richard Locksley, a professor at the University of California at San Francisco, who studies the same types of immune cells.

“It’s the start, but it’s interesting and plausible,” he said.

Scientists at Penn stimulated mouse immune cells by treating them with a type of cytokine – the same family of proteins involved in a harmful inflammatory response to COVID-19, called a “cytokine storm.” Scientists persuaded the animals to produce the cytokine by injecting them with a viral vector, loaded with genetic instructions to make the protein – much like the COVID-19 vaccine made by Johnson & Johnson.

If the concept were to be explored in humans, researchers would likely try to achieve the same goal – increasing the production of this cytokine, called TSLP – by administering a drug instead of genetic instructions, he said.

Researchers are already testing drugs that achieve the opposite goal, interfering with TSLP, as a possible treatment for atopic dermatitis. Commonly known as eczema, the skin condition is triggered by an overreaction of the immune system.

Increasing TSLP, on the other hand, should be done with caution, lest it lead to an inappropriate immune response. Kambayashi is already laying the groundwork for follow-up studies in people.

For the results released Thursday, most of the lab work was done by Choa, who earned her doctorate. in 2020 and is now completing her MD at Perelman, Kambayashi said.

“She easily did the work of three people in a year and a half,” he said. “She was on a mission.

Among the remaining questions is how the cytokine causes excessive secretion of sebum. The researchers found that TSLP causes certain types of immune T cells to migrate to the sebaceous glands, which somehow results in more secretions.

Regardless of the outcome of these studies, Kambayashi said that with hindsight, it makes sense that obesity can be treated by the immune system.

As doctors reminded us during the COVID-19 pandemic, obesity is often accompanied by a chronic level of inflammation related to the immune system. Excess fat tissue acts as a type of “organ,” releasing hormones and other chemicals that put the body in a chronic state of low stress, which puts the person at a higher risk for it. cases of infection.

Still, the weight loss in the mice came as a surprise, to the point that Kambayashi thought something must have gone wrong.

“I thought they were sick, that they just weren’t eating,” he said.

But in fact, they ate more than the mice in a control group, which had not been treated with the cytokine.

The key clue came with a curious phenomenon that Kambayashi and others had overlooked in the past: Mice treated with TSLP were known to develop a shiny coat.

He and Choa noticed that the same was true with these mice. So they shaved the animals’ fur, analyzed it, and found it to be rich in high-calorie fatty molecules called wax esters.

Would humans sign up for this type of treatment knowing that it would increase the secretion of fatty fats through the skin? Among the possible drawbacks: Excess sebum is associated with the adolescent scourge of acne.

Yet, with obesity among the top health problems in the United States, millions of people remain eager to try new solutions. Kambayashi says he’s determined to give them the chance.

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