Researchers give mice super calorie-burning fat cells with CRISPR


Mice hide in a loaf of bread.

Mice hide in a loaf of bread.
Photo: YOSHIKAZU TSUNO / AFP (Getty Images)

Researchers say they have found a way to make more useful fat cells with the geneediting technique CRISPR. In a new study Wednesday, they found evidence — in mice — that these engineered cells could possibly burn the body faster, as obesity and other metabolic problems occur, compared to the most common fat cells in the human body. But the findings are still a long way from being applied to humans.

Yu-Hua Tseng, a diabetes researcher at Harvard Medical School, and her lab have been studying the complexity of fat cells for years, focusing on the difference between so-called white and brown fat cells (the brown color comes from the higher levels of mitochondria). have them, which contain a lot of iron). The primary purpose of white fat cells is to store energy the food, while healthy suns are primarily thought to be used as a way to keep our body temperature stable, especially in the cold.

Scientists like Tseng have shown that brown fat cells are better at breaking down the nutrients they process than white fat. But most of the fat in the body is white, not brown, and many people now have an excess of body fat, leading to health problems such as obesity and type 2 diabetes. As a result, Tseng and her team have theorized that if we find a way to to make white fat cells safely brown, that should help treat or prevent obesity.

In this new study, published On Wednesday in Science Translational Medicine, Tseng and her team appeared to do just that. Using CRISPR, they made changes to precursors of human white fat cells. The changes turned on the white fat cells express a protein mostly produced by brown fat cells and thought to be key to their improved energy burning skills, known as decoupling protein 1 (UCP1). Then they transplanted into these human brown-like cells – codenamed HUMBLE cellsto obese mice fed a fatty diet and documented with what happened to them compared to a control group of mice that received human white fat cells through transplantation and a third group of mice with transplanted brown fat cells.

Above, the mitochondria of white, HUMBLE and brown fat cells, as seen in experiments by Tseng and her team with mice.

Above, the mitochondria of white, HUMBLE, and brown fat cells, as seen in experiments by Tseng and her team with mice.
Image: Chih-Hao Wang, et al / Science Translational Medicine

Tseng and her team found that the mice with HUMBLE cells were better across the board than the mice with white fat cells and would have the same results as the mice with brown fat cells. The internal structure of HUMBLE cells also looked more like brown fat cells, especially when it came to their mitochondria.

“They can clear their glucose much faster; they may respond better to insulin. En in terms of weight gain they can gain less weight compared to the control mice, ‘said Tseng by phone. “That all means an improvement in their metabolism.”

These experiments are a proof-of-concept for researchers like Tseng, not something that will be tested in humans in clinical trials soon. We are now only beginning to see the very slightest tears of CRISPR in humans for diseases such as cancer and muscular dystrophy, although the results so far have been encouraging.

There are inherent restrictions to the approach that Tseng and her team used in this study. For example, the mice were immunocompromised to ensure that the human cells were accepted without problems. The cells used were also cultured from the cell lines of only two people. It is possible that a native immune system may affect how HUMBLE cells work, as these cells can harvest from a larger number of people, the authors stated.

But by successfully making these cells and studying how they make mice healthier, Tseng said, we will come much closer to finding an effective way to help reduce or prevent humans. overweight. This can happen through genetic engineering or through a drug that can mimic its effects on white fat cells, she added. Already in this study, the team found evidence that these HUMBLE cells increase the production of nitric oxide in the blood, which in turn can activate natural brown fat cells elsewhere in the body (in another study, reduced production of nitric oxide linked to obesity).

In addition to studying these HUMBLE cells in the lab more closely, Tseng is also trying to work with them. researchers and clients in other fields.

“To apply this once to patients, we need a team with different expertise. I can certainly not achieve that myself, ‘she said. “But I really hope our research can ultimately benefit patients.”

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