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SAN FRANCISCO — Have you ever wondered why losing weight or maintaining a healthy body weight can be such a challenge? A new study published in the Journal of Clinical Investigation may hold some answers. Researchers from UC San Francisco have unveiled the critical role of a protein called KLF15 in regulating fat cells, potentially opening new doors for treating obesity and metabolic diseases.
In a nutshell, the researchers have found a way to switch off this protein within white fat cells. This is the type of fat people carry in abundance, which stores up calories. By switching off KLF15, the white fat turns to beige fat cells, which burns calories.
“A lot of people thought this wasn’t feasible,” says Brian Feldman, MD, PhD, the Walter L. Miller, MD Distinguished Professor in Pediatric Endocrinology, in a university release. “We showed not only that this approach works to turn these white fat cells into beige ones, but also that the bar to doing so isn’t as high as we’d thought.”
Calorie-storing white fat cells. Image by Liang Li.
Methodology: How the Study Was Conducted
At the heart of this study lies the investigation into white and brown adipose tissue, which are types of body fat that function differently. White adipose tissue (WAT) stores energy, while brown adipose tissue (BAT) burns energy and generates heat. Researchers focused on a particular protein, KLF15, which they suspected played a crucial role in maintaining the properties of white fat cells in subcutaneous (just under the skin) fat depots.
Using advanced genetic techniques, scientists developed mice models where the KLF15 protein could be selectively deleted from certain fat cells. This allowed the researchers to observe what happens when KLF15 is absent and how it affects the behavior of fat cells under various conditions, including cold exposure and beta-adrenergic stimulation, which typically activates fat burning in brown adipose tissue.
Ordinary white fat, which is common and stores calories to keep energy reserves in the body. Image by Liang Li
Key Results
The findings were quite revealing. When KLF15 was deleted from white fat cells, these cells began showing characteristics typical of brown fat cells, such as increased fat burning and heat production. This transformation was particularly notable in subcutaneous white adipose tissue. The study demonstrated that without KLF15, white fat cells increase their expression of a specific receptor (β1-adrenergic receptor), which plays a pivotal role in this conversion process.
Furthermore, the transformed cells showed higher metabolic rates, indicating that they were burning energy more actively, mimicking the behavior of brown fat cells. This process, known as “browning,” has been a significant area of interest because it suggests a possible way to increase energy expenditure and fat burning in the body.
“For most of us, white fat is not rare and we’re happy to part with some of it,” Dr. Feldman says.
White fat without the KLF-15 protein, which contains small patches of calorie-burning beige fat cells (seen above in the beige areas within the black circle). Image by Liang Li
Discussion & Takeaways: Why This Matters
By understanding the role of KLF15 in fat cell behavior, researchers can explore new treatments for obesity that involve altering this protein’s activity within our cells. The ability to convert white fat into beige fat could revolutionize how we treat obesity and related conditions, offering a method to burn more calories naturally.
“We’re certainly not at the finish line, but we’re close enough that you can clearly see how these discoveries could have a big impact on treating obesity,” Dr. Feldman concludes.
