White fat cells can be turned into energy-burning brown fat using CRISPR gene-editing technology. These engineered cells have helped mice avoid weight gain and diabetes when on a high-fat diet, and could eventually be used to treat obesity-related disorders, say the researchers behind the work.
Human adults have plenty of white fat, the cells filled with lipid that make up fatty deposits. But we have much smaller reserves of brown fat cells, which burn energy as well as storing it. People typically lose brown fat as they age or put on weight. While brown fat seems to be stimulated when we are exposed to cold temperatures, there are no established methods of building up brown fat in the body.
Yu-Hua Tseng at Harvard University and her colleagues have developed a workaround. The researchers have used the CRISPR gene-editing tool to give human white fat cells the properties of brown fat.
Tseng and her colleagues used CRISPR to target a gene for a protein called UCP1, which is uniquely expressed in brown fat. “Its function is basically to turn chemical energy into heat,” says Tseng. The resulting cells more closely resembled brown fat cells – they expressed almost as much UCP1 as typical brown fat cells and had more mitochondria than typical white fat cells. The researchers called them human brown-like cells, or HUMBLE cells.
In a second part of the study, Tseng and her colleagues transplanted either white fat, brown fat or HUMBLE cells into mice bred to have a weakened immune system that wouldn’t reject human tissue. All of the mice were then fed a high-fat diet.
Over a 12-week period, the mice given white fat cells gained weight, and Tseng says they would likely have shown signs of diabetes had they been typical, healthy mice. But the mice transplanted with either brown fat or HUMBLE cells gained significantly less weight. These mice were also more sensitive to insulin, suggesting they might be protected against diabetes, says Mark Christian at Nottingham Trent University in the UK, who wasn’t involved in the study.
In the future, this technique could potentially be used to treat people affected by obesity and metabolic disorders, says Tseng. It could be possible to remove a small amount of a person’s white fat, engineer it into brown-like fat and re-implant it, she says.
Such a treatment could be an option for people who are unable to lose weight with diet and exercise alone, says Tseng, although she stresses that more research is needed before human studies begin.
It also raises the possibility of other approaches to weight loss and diabetes prevention, says Christian. Tseng’s team found that the transplanted HUMBLE cells seemed to send a chemical signal to the mice’s existing stores of brown fat, stimulating them to burn more energy. Mimicking this signal to activate the body’s own brown fat could provide a simpler treatment approach, says Tseng.
Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.aaz8664
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