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Long viewed as a metabolic villain in diseases like diabetes, fat is showing its hero side. A groundbreaking study published in the journal Cell by molecular biologist Shingo Kajimura and his team reveals that brown fat, a type of fat tissue, improves metabolic health by providing essential nutrients to other organs rather than merely generating heat.
Revisiting Brown Fat’s Role
The traditional view of brown fat is that its primary benefit is generating heat by burning calories, thus improving metabolism. Kajimura, a Howard Hughes Medical Institute Investigator at Beth Israel Deaconess Medical Center, questioned this assumption. “The field has assumed that brown fat’s metabolic benefits are simply due to its ability to generate heat by burning calories,” says Kajimura. “But is this really all it does?”
The new research suggests otherwise. Kajimura’s team demonstrated that brown fat breaks down amino acids to supply crucial nutrients that protect blood sugar metabolism, providing a fresh perspective on its benefits.
Brown Fat’s Beneficial Mechanism
The human body requires warmth to function properly. To maintain internal temperature in cold conditions, we either shiver or activate our brown fat. Once believed to be exclusive to infants, brown fat is also present in adults, particularly along the spine and neck. The distinctive color of brown fat comes from its high concentration of mitochondria, cellular structures that generate energy from sugar and fat.
Traditionally, it was believed that brown fat’s furnace-like function—burning calories to generate heat—was the sole reason for its metabolic benefits. This function was thought to enhance the body’s ability to manage sugar, fat, and cholesterol, thereby reducing the risk of conditions like type 2 diabetes and cardiovascular diseases.
However, research, including work from Kajimura’s lab, suggested brown fat might have additional roles. A 2019 study hinted at this by showing that brown fat breaks down branched-chain amino acids (BCAAs). Although BCAAs are vital for protein production and antioxidant formation, high levels in the blood are associated with diabetes and obesity.
Linking Brown Fat and the Liver
In the new study, Kajimura’s team explored the connection between brown fat and BCAAs by disabling brown fat’s mitochondria in cells and mice. The inability to break down BCAAs resulted in decreased glutathione—a crucial antioxidant—leading to liver stress. This stress impaired blood sugar control, a hallmark of type 2 diabetes, but could be reversed by supplementing with glutathione.
Study co-author Takeshi Yoneshiro, an associate professor at Tohoku University, extended these findings to humans. In an experiment, 33 men were exposed to a mildly cold environment (19°C or 66°F) for two hours. This exposure not only increased brown fat activity but also boosted glutathione production.
While these findings highlight the liver’s role in sugar metabolism, James Lo, an associate professor of medicine at Weill Cornell Medicine, suggests brown fat might influence other bodily processes, including those in muscles or the pancreas. “There may be other things brown fat can do from a metabolic perspective,” he says.
Activating Brown Fat Without Cold Exposure
Although cold exposure activates brown fat, researchers are seeking alternative methods to harness its benefits without the discomfort and potential cardiovascular risks associated with cold. “First, it’s not comfortable, I hate being cold,” Kajimura says. “The second problem is that it can be bad for your heart, because it makes blood pressure go up.”
Kajimura’s lab is now investigating chemical-based methods to mimic cold’s effects on brown fat, leveraging their new understanding of its role in amino acid metabolism to find safer, more comfortable ways to activate brown fat’s metabolic benefits.
The study, BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis, by Anthony R.P. Verkerke et al., represents a significant step forward in understanding the diverse roles of brown fat in metabolic health.
