Once thought of as inert tissue, fat – or adipose tissue – is now known to play an active role in critical body functions by secreting hormones that regulate hunger and body temperature. Body fat comes in many varieties; for example, white adipose tissue stores excess energy and brown adipose tissue primarily burns energy. Over the past decade, researchers have isolated a new type of fatty tissue called beige adipose tissue. Beige fat cells begin life as white fat cells, but take on the characteristics of energy-burning brown fat cells under certain circumstances.
A growing body of evidence suggests that brown and beige adipose tissue protects against metabolic diseases, such as insulin resistance and diabetes. Increased production, or biogenesis, of energy-burning beige fat has been associated with substantially improved metabolic health. Now, researchers at Beth Israel Deaconess Medical Center (BIDMC) have developed a transformative approach to making more of this cell type. They identified a key enzyme, Cul2-APPBP2, which catalyzes the degradation of the PRDM16 protein, a potent activator of beige fat biogenesis. The book is available online in the journal Nature.
“The best-known approach to inducing beige fat biogenesis is chronic cold acclimation; however, chronic cold acclimation can be dangerous due to elevated blood pressure, in addition to the fact that exposure to cold is uncomfortable for most people,” said corresponding author Shingo Kajimura, Ph.D., a Howard Hughes Medical Institute researcher in the BIDMC’s Division of Endocrinology, Diabetes and Metabolism. “This work brings a completely new solution by proposing a control model of the biogenesis of beige adipocytes.”
Based on previous work suggesting that the PRDM16 protein plays a key role in beige fat biogenesis, the researchers conducted a series of experiments to determine how protein turnover was controlled in white fat cells in mice. A decade-long discovery, Kajimura and his colleagues have identified the key enzyme – an E3 ligase complex named CUL2-APPBP2 – that breaks down protein in fat cells.
In the absence of the E3 ligase complex, the PRDM16 protein activated heat-producing genes characteristic of beige fat, counteracting diet-induced obesity, glucose intolerance, insulin intolerance and abnormal blood fat levels in mice. Scientists also observed that the protein suppresses damaging pro-inflammatory genes in fat cells, suggesting another pathway by which brown and beige fats contribute to metabolic health.
“We hope that an inhibitor will be an effective approach to stimulate beige fat biogenesis and improve metabolic health safely,” said first author Qiang Wang, an instructor in Kajimura’s lab. “We are now looking for specific inhibitors to block the E3 ligase complex.”
Exposure to cold, capsinoids promote the biogenesis of beige adipocytes
Shingo Kajimura, Post-translational control of beige fat biogenesis by PRDM16 stabilization, Nature(2022). DOI: 10.1038/s41586-022-05067-4. www.nature.com/articles/s41586-022-05067-4
Quote: Researchers identify key enzyme that controls conversion of white fats to brown (2022, Aug 17) Retrieved August 17, 2022 from https://medicalxpress.com/news/2022-08-key-enzyme-white-to- brown-conversion-grease.html
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