Type 2 Diabetes Research in the Guertin Lab Tracked and Discovered New Functions of Glucose in Brown Fat
Date Posted: Thursday, September 09, 2021
Obesity is the leading risk factor for type 2 diabetes. One of the research goals of David Guertin, PhD at the UMass Chan Medical School is to understand adipose (fat) tissue and the role it plays in metabolism. Brown adipose tissue (BAT), commonly known as brown fat, is a type of body fat that is activated in cold conditions. Its main function is to turn the energy from fat storage and food into heat that helps maintain body temperature in the cold. It’s known that active brown fat consumes and uses a lot of glucose (and other nutrients). This has provoked the exciting idea that triggering brown fat activity with drugs could be a potential therapeutic strategy to treat diabetes, hyperglycemia, obesity, etc. However, until recently, it was unclear how brown fat actually used the glucose it consumed.
In a new study published in Cell Reports, the Guertin Lab learned that BAT uses glucose not only for fuel, but for many other metabolic pathways that support heat production (also called thermogenesis). This was possible through adapting a new technique and strategy to track how brown fat uses the individual atoms of glucose as they are consumed by the brown fat tissue.
Brown Adipose Tissue (BAT)
We know that newborn babies, small mammals, and hibernators have high levels of BAT to help protect them against cold, however, its role in adult humans is still being worked out. BAT was first discovered in adult humans in 2009 during FDG-PET-CT scans looking for metastatic cancers. The fact that brown fat uses a lot of glucose was the basis for its detection. However, scientists still don’t understand the biology of how that blood sugar is used.
Glucose Tracking in Brown Fat
Glucose has long been known to provide energy and heat production (thermogenesis), but this study shows that it has other purposes as well.
Su Myung Jung, PhD, and research assistant Will Doxsey led the study in collaboration with Cholsoon Jang's lab at UC Irvine with an MD/PHD student, Johnny Le. Doxsey was excited to be on the first team to explore the pathways of glucose, comparing it to being a cartographer for metabolism and creating a map of the unknown. Dr. Jung used the analogy of putting a GPS tracker on the glucose and they discovered that it traveled more routes than anyone originally thought.
“This is the forefront of understanding how organs use nutrients in vivo in a physiological context,” said Dr. Guertin, a professor in the program in molecular medicine at UMass Chan Medical School. “These techniques have been accomplished in cultured cells for some time, but we’ve now developed the methods to do it in a whole mouse, which is a great model of human brown fat biology.”
The conventional thinking was that BAT took up glucose and other nutrients and simply burned it all immediately to create heat, but they wondered if the glucose may be serving other purposes. They indeed uncovered several functions of glucose not previously known to play a role in thermogenesis. They learned that glucose is converted into other molecules the help support brown fat function.
“It’s exciting to work on the first team in the world to optimize this tactic to study brown adipose tissue,” said Dr. Jung. “Obtaining the data we were able to collect, plus what we observed, makes this project double exciting!”
“It’s the first time it’s been applied on this level to BAT,” added Dr. Guertin. “Combining this technique with our expertise in adipose tissue biology has us excited for future explorations of in vivo brown fat metabolism.”
A Catabolic Cell First Performing Anabolic Metabolism
Metabolism can either be catabolic or anabolic. The major difference is how the molecules are utilized in the body. Anabolism creates molecules the body needs to function, and it uses energy in the process. Catabolism breaks down complex molecules and releases energy for the body to use.
Classic thinking was that thermogenic cells use glucose for mainly catabolic purposes, mainly to fuel heat production. This study shows that glucose is also synthesized into other macromolecules including lipids through an anabolic pathway, which are then broken down and used as fuel. Why this happens is still unknown.
“We’re now very curious to why that is and plan to explore it further,” said Dr. Guertin. “Interestingly, it is quite similar to the metabolism of many cancer cells.”
Glucose has been shown to produce and burn lipids and other metabolites that are created and used when the body breaks down food or its own tissue, in this case brown fat. In future experiments they plan to further explore the newly discovered glucose driven pathways to understand their roles and importance.
As previously mentioned, cold temperature activates brown fat, but this study showed that both the degree and duration of temperature can affect how the glucose is used. It also identified several metabolites that increase in abundance when BAT is activated, leaving more questions to be answered.
What’s Next?
The data produced in this study opens the door for plenty of future investigation about the role of these new metabolic pathways they discovered in brown fat. “This paper provides a new map of information for scientists worldwide to explore unknown territory that’s ripe for discovery,” said Dr. Guertin. “We’ve also provided the approach and methodology by which to study it.” The Guertin lab will continue to learn more about glucose and other nutrients and how they are used by brown fat. Hopefully scientists can use this better understanding of brown fat metabolism to discover options to activate the tissue as means of fighting obesity and diabetes.
Su Myung Jung, PhD
Dr. Jung spent nearly five years as a post-doctoral fellow in the Guertin lab, where he was funded by the American Diabetes Association. He recently accepted a faculty position at his alma mater, Sungkyunkwan University in South Korea where he earned his undergraduate and PhD degrees in molecular cell biology. With his own independent lab, Dr. Jung looks forward to future collaborations with the Guertin lab studying brown fat metabolism and mTORC2 signaling.
Will Doxsey, Research Assistant
Will is a research technician who recently graduated from UMass Amherst with his sights set on graduate school. He received high praise from Dr. Guertin who said, “Will is a gifted young scientist with a bright future in research.” His goal is to someday have his own independent research lab.