A key gene that acts as a “brake” on an energy-burning type of fat could be key to understanding how to activate fat burning and potentially how to encourage fat burning in the body.
Dr. Weiqin Chen at Augusta University has grants totaling $2.16 million to study a particular gene for Berardinelli-Seip Congenital Lipodystrophy 2 or BSCL2, which has been implicated in a rare condition where people don’t have fat in their bodies. Chen has been studying it since 2007 but recently discovered it has a connection with brown fat, a hot area of research because it is a type of fat that burns energy and creates heat.
The fat was known to be in animals that hibernate and in human babies but was thought to be absent in adults until recently, when deposits of it were detected. Besides the more common white fat that stores energy and accumulates in deposits, there is a closely related but distinct type of other fat called beige that can form within white fat deposits and is also energy-burning and heat producing.
Scientists found that they could produce and activate these energy-burning fats by exposing animals to the cold, for instance. But figuring out how to harness them as therapies for humans has proven elusive. For instance, scientists noted that the brown fat could be activated by stimulating receptors for the sympathetic nervous system, which activates the “fight or flight response” in the body, but therapies to do that proved unsuccessful because of the side effects.
“With long-term treatment with the (therapies), definitely you can lose weight, but it increases the heart rate and blood pressure and ultimately causes heart problems,” Chen said.
But Chen found when she bred mice to lack the BSCL2 gene, brown fat was activated to burn fat, and yet it did not appear to activate the sympathetic nervous system. Also, when the gene was deleted from mature white fat cells, it induced the energy-burning beige fat, Chen said.
“Those mice then become lean and lose white fat because they have more beige fat that starts burning in those white fat (deposits),” she said. “We thought that would be an interesting therapeutic target. It just means this gene definitely plays a role in inducing beige fat. We definitely observed the fat loss in mature white fat in adult mice.”
It is clear to her that it is involved in fat synthesis and formation.
“It’s like a brake,” Chen said. “But when you remove that brake, then everything starts burning. Your mature white fat, brown fat, everything starts burning. You start to lose fat mass.”
It is important to have it early on, she said.
“You need it during the development stage because without it you will not have any fat formation,” Chen said. But in adult animals it appears to have those beneficial effects.
Much of her work is in the early stages. While she is looking at its role in fat, other researchers believe the gene is involved in calcium signaling.
It is unclear what the gene’s target ultimately is and what might be normally regulating the gene. Chen uses a fluorescent protein that can glow green to tag the gene, then looks at cells under a fluorescent microscope to study where it might be active within the cell to get a better idea of how it is working.
“What we are studying is a very important pathway that regulates fat biology,” Chen said. “It’s a little bit far away to say it could be directly translational right now.”
She started looking at this gene before brown fat became a desirable research subject, and now she is part of a growing field.
“It’s a very new, hot field,” Chen said. “From my point of view, I just want to understand how this gene works because it is very important in all kinds of fat.”