Cellular atlas will provide an important resource for translational research into human metabolic diseases, including type 2 diabetes
Researchers catalog white fat cell types present in mice and in humans
Once considered inert, white adipose tissue (or white fat) is now recognized to be dynamic and to play interactive roles in a wide array of biological and metabolic processes. Diet and energy expenditure can cause dramatic changes to the physiology, behavior, and cellular make-up of white adipose tissue, and these changes, in turn, are linked with metabolic diseases, including type 2 diabetes.
Now, scientists at Beth Israel Deaconess Medical Center (BIDMC) and the Broad Institute of MIT and Harvard have generated an atlas of the cell types present in the white adipose tissue of humans and of mice, allowing them to explore the composition of white fat in unprecedented detail. Their work describes novel subpopulations of fat cells, and links specific cell types to increased risk of metabolic disease. The team’s findings, published in the journal Nature, lay the groundwork for future studies of the complex underpinnings of body weight, metabolism, and disease.
"We provide an initial blueprint for a comprehensive set of interactions between individual cell types in white adipose tissue, across individuals at different body weights," said Evan Rosen, who is the chief of the Division of Endocrinology, Diabetes, and Metabolism at BIDMC, and an institute member in the Metabolism Program at Broad. "Our first-of-its-kind data set provides a rich resource to identify other disease-associated cell types and to better interpret genetic studies related to metabolic disease."
Rosen and colleagues (including study first author Margo Emont, a postdoctoral fellow in the Rosen laboratory) identified cell types in adipose tissue taken from both men and women, across a wide range of body weight. As adipose tissue can have different properties depending on where in the body it is located, Rosen’s team generated their atlas from fat located in two different locations: beneath the skin (subcutaneous fat) and in the abdominal cavity (visceral fat). They were able to show that the composition of fat differs between these locations, and also changes considerably in obesity. Among the most striking findings was the discovery of new subtypes of human white adipocytes, some of which are associated with conditions like type 2 diabetes.
Because many adipose tissue researchers use mice as a model, Rosen’s group also generated a mouse adipose atlas, again looking at males and females, lean and obese, and visceral and subcutaneous fat. In general, mouse adipose tissue was very similar to human, with a few key differences.
"Our work provides a framework for mouse-human comparison in studies of adipose tissue that will be an important resource for groups hoping to translate mouse findings to human treatments," said Rosen, who is also a professor of medicine at Harvard Medical School. "Our data provide a lens of unprecedented acuity that better informs our understanding of white adipose tissue biology and enables a deeper exploration of its role in health and disease."
Support for this study came from the National Institute of Diabetes and Digestive and Kidney Diseases and other sources.