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Mice reveal role of human brown fat
In a paper published in the Journal of Clinical Investigation Insight, a team of researchers from several institutions, including Baylor College of Medicine, opens the door to a future of using brown fat to treat metabolic conditions such as obesity and type 2 diabetes.
""In addition to white adipose tissue, or white fat, people have brown fat, an important contributor to the body's energy balance via the generation of body heat and the participation in metabolic processes."
Brown fat contains adipocytes, cells rich in small fat-filled droplets and energy-producing structures called mitochondria. Brown fat adipocytes use fat and glucose as sources of energy. In mice, brown fat activated to produce heat dramatically affects energy balance. For example, mice housed at temperatures below their own normal body temperature (20-22 degrees Celsius or 70-74 degrees Fahrenheit) would need to consume 60 percent more food to maintain a normal temperature as compared to mice housed at 30 C or 86 degrees Fahrenheit. Other experiments have shown that when brown fat is dysfunctional or absent in mice, they decrease their energy expenditure and become obese.
Previous studies had indicated that most brown fat in mice is on their back, between their shoulder blades. In people, however, our main brown fat deposits are located above our collar bones and deep in our neck.
However, when Chen and her colleagues analyzed mouse embryos, they found brown fat in their neck surrounded by muscles, including a brown fat deposit located above their collar bones, the same location as human brown fat.
"Further studies showed that adult mice also have brown fat above the collar bones. This is important because studies will be carried out mostly in adult mice. In addition, mouse brown fat in the collar bone is morphologically similar to human brown fat in the same location, produces compounds involved in the production of heat and expresses genes similar to those expressed by human brown fat."
When researchers increased the amount of brown fat above the collar bone by transplanting it into healthy mice, they saw improvement in the animals' glucose tolerance.
"This shows that this brown fat deposit, which is remarkably similar to the main brown fat deposits in humans, can be metabolically beneficialó highlighting how important this tissue most likely is in humans."
Dr. Stanford:"For several years, I've been interested in how to combat obesity and improve metabolic health. A few years ago, my lab developed a transplantation model looking at the effects of increasing brown fat above the shoulder blade in mice, and we saw a dramatic improvement in metabolic health. When Dr. Chen showed me her data identifying brown fat above the collar bone in mice, I was excited to collaborate and apply our transplantation model."
"I am most excited to bring this model to scientists in the field so they can use it to study brown fat," Chen adds."This model is the first step to improve our understanding of the role of human brown fat in metabolic processes."
A fundamental challenge to our understanding of brown adipose tissue (BAT) is the lack of an animal model that faithfully represents human BAT. Such a model is essential for direct assessment of the function and therapeutic potential of BAT depots in humans. In human adults, most of the thermoactive BAT depots are located in the supraclavicular region of the neck, while mouse studies focus on depots located in the interscapular region of the torso. We recently discovered BAT depots that are located in a region analogous to that of human supraclavicular BAT (scBAT). Here, we report that the mouse scBAT depot has morphological characteristics of classical BAT, possesses the potential for high thermogenic activity, and expresses a gene signature that is similar to that of human scBAT. Taken together, our studies reveal a mouse BAT depot that represents human BAT and provides a unique tool for developing new translatable approaches for utilizing human scBAT.
The authors have declared that no conflict of interest exists.
Other contributors to this work include Qianxing Mo, Jordan Salley, Tony Roshan, Lisa A. Baer, Francis J. May, Eric J. Jaehnig, Adam C. Lehnig, Xin Guo, Qiang Tong, Alli M. Nuotio-Antar, Farnaz Shamsi Yu-Hua Tseng. The authors are affiliated with one of more of the following institutions, Baylor College of Medicine (BCM), The Ohio State University Wexner Medical Center, Rice University and Harvard Medical School.
This study was supported by USDA/ARS CRIS3092-5-001-059, National Institutes of Health (NIH) P30-DK079638, the American Heart Association 16GRNT30720003 and NIH K01-DK105109. RNA sequencing and data analyses were supported in part by the Genomic and RNA Profiling Core at BCM with funding from the NIH Center grant (P30-DK079638). TEM analyses were supported by the Integrated Microscopy Core at BCM with funding from the NIH (HD007495, DK56338 and CA125123).
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