Researchers identify cellular origins of fat

fat cells
Photo by Karen Tian.

Yale researchers have identified a population of cells that eventually develop into adipocytes, or the cells that make up fat tissue.

A study led by Ryan Berry GRD ’15 and associate research scientist Matthew Rodeheffer from the Yale School of Medicine determined that a specific type of cell, the CD24+ cell, differentiates into fat cells in mice. This development answers many questions regarding the origins of body fat, which is the key factor in highly prevalent conditions such as diabetes and obesity. Berry and Rodeheffer published their findings in the Feb. 24 online issue of the journal Nature Cell Biology.

“One of the things that hadn’t been figured out is exactly what the cell lineage is, or ‘Where do fat cells come from in the body?’ The whole point of this paper was to nail down and identify what cells actually make the fat cells in the body,” Rodeheffer said.

For the study, which occurred over roughly two and a half years, Rodeheffer and Berry marked one cell population in each mouse subject with fluorescent proteins. Over time, the researchers were able to identify which group of cells eventually differentiated into adipocytes by looking for fluorescence in the fat tissue that developed in each mouse. Ultimately, it was the mice in which CD24+ cells — cells that express the PDGF receptor alpha — were tagged that showed fluorescence in their adipose tissue, and further tests confirmed that these cells did indeed develop into fat cells.

“By showing that adipocytes derive from cells that express PDGF receptor alpha, we can actually look at what genes those specific cell types express and potentially modulate how fat is formed or to activate or deactivate these cells from being able to differentiate to form new adipocytes,” Berry said.

The implications of this study are far-reaching, researchers said. By understanding the original form from which fat cells develop, researchers can now investigate and potentially decelerate the processes by which fat grows, Berry said. Conversely, there also is the possibility of synthesizing fat tissue for the sake of reconstructive surgery in a process similar to culturing skin cells to create skin grafts.

“What’s really of interest is what actually activates these precursor cell populations. We know that when you place animals on a high-fat diet, they grow, they get overweight just like humans do when they eat too many calories,” Berry said when asked about the next steps in this study. “We’re actually probing to ask the question of what exactly in high-fat diets activates these cell populations and leads to accumulation of adipose tissue.”

Professor Robert Farese of the University of California, San Francisco’s Diabetes Center, who worked with Yale researchers who analyzed fat storage methods, said Berry and Rodeheffer’s work will be important in the quest to understand adipogenesis, the full process by which fat cells are synthesized.

“We know that increases in fat leading to obesity involves both growing existing fat cells and making new fat cells. To understand how they are made anew, we have to understand where they come from. So, this paper is an important step,” Farese said.

More than one-third of adults in the United States are considered obese, according to the Centers for Disease Control and Prevention.

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