A team of American researchers has discovered how to transform white fat cells that contribute to obesity into beige fat cells that burn calories. This finding could explain why previous clinical trials for related treatments have failed, and it holds promise for new weight loss drugs.
A team led by Professor Brian Feldman of the University of California, San Francisco, announced on Tuesday in the Journal of Clinical Investigation that limiting the production of a specific protein can turn white fat into beige fat.
Humans and other mammals possess three types of fat cells: white, brown, and beige. White fat functions primarily to store calories. In contrast, brown fat helps maintain body temperature by burning energy. Beige fat, similar to brown in its calorie-burning function, is unique in that it accumulates among white fat cells.
Like other mammals, humans are born with brown fat, mostly disappearing within the first year of life. However, exposure to cold environments or adhering to specific diets can convert white fat into beige fat.
Scientists have long tried to develop obesity drugs to turn white fat into brown or beige fat but have not been successful. Feldman said, “Many people have tried to create brown fat from stem cells. In this study, we wanted to find a switch that directly converts white fat cells into beige fat cells.”
The research team focused on a protein called KLF-15, vital in metabolism and fat cell function. Upon investigating how KLF-15 functions in mice, whose brown fat remains throughout their lives, they found KLF-15 is more abundant in white fat cells than brown or beige fat cells. When they created mice with white fat cells deficient in KLF-15, they observed that the body’s white fat was converted into beige fat.
The researchers also discovered that KLF-15 regulates the amount of a receptor called Adrb1, which maintains energy balance. The team noted that scientists had previously found that stimulating the Adrb3 receptor in mice reduced their weight. After failing clinical trials on drugs that act on this receptor, this research shows that the target of these drugs was incorrect.
Feldman mentioned that drugs targeting the human Adrb1 receptor have a strong potential for effectiveness, noting that these could offer significant advantages over newer injectable weight loss drugs that act by suppressing appetite and blood sugar. He emphasized that this approach targets fat accumulation without influencing the brain, which could help avoid side effects. He acknowledged that while the finish line has not yet been reached, the discovery holds substantial promise for impacting obesity treatment.
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