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Composition of adipose tissue may point to new treatment pathways


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C. Ronald Kahn, MD
C. Ronald Kahn, MD

Emerging research suggests that the composition of adipose tissue may be more important in terms of insulin sensitivity and personal diabetes risk than the quantity of fat an individual carries.

“There has been a progression in our thinking about the interaction between adipose tissue and metabolism and diabetes,” said C. Ronald Kahn, MD, Chief Academic Officer at the Joslin Diabetes Center and the Mary K. Iacocca Professor of Medicine at Harvard Medical School.

“Over the last few years, our ability to look at fat has gotten to be ever more sophisticated,” he continued. “While fat cells may look alike in terms of having this big drop of lipid storage, they’re not all alike. Each fat depot appears to be composed of fat cells with different functions, such that, depending on the composition, some adipose tissue can put you at higher or lower risk of metabolic disease. It’s all about how the heterogeneity of fat cells makes a difference.”

Dr. Kahn is chair of Tuesday’s symposium Adipose Tissue at the Single-Cell Level, which will begin at 7:30 a.m. in S-157 (South, Upper Mezzanine Level).

Yu-Hua Tseng, PhD
Yu-Hua Tseng, PhD

Adipose tissue, like so many other organs, is composed of multiple cell types. Different types of adipocytes exert different effects on metabolism.

“To look at adipose tissue at the single-cell level is critical for obtaining a deeper understanding of the function of adipose tissue and adipose cell development,” said Yu-Hua Tseng, PhD, Principal Investigator in the Section on Integrative Physiology and Metabolism at Joslin Diabetes Center and Associate Professor of Medicine at Harvard Medical School.

“If we can generate more of the type of fat cells that burn more energy than they store, for example, it could be a very attractive way to treat obesity and everything related to it, including type 2 diabetes,” she explained. “As we learn in great detail about the secretory function of different types of adipocytes, we are likely to uncover more potential drug targets.”

Exploring adipose tissue at the cellular level is also uncovering previously unknown cell types. While looking for the progenitors of adipocytes, researchers recently discovered a novel type of cell that appears to block formation of new fat cells.

“We called these adipogenesis regulatory cells, or Aregs for short,” said Bart Deplancke, PhD, Associate Professor and Swiss Institute of Bioinformatics Group Leader at the Swiss Federal Institute of Technology in Lausanne, Switzerland.

Bart Deplancke, PhD
Bart Deplancke, PhD

As fat mass expands, typically in response to excessive calorie intake, the body produces more fat cells to spread the stored energy across more cells. The hypothesis now is that, at some point, Aregs may block formation of new fat storage cells, with the additional energy stored as ever-larger lipid depots in existing fat cells or even other tissues.

“Very simply put, if you feed yourself too many calories, you have high levels of insulin in your system,” Dr. Deplancke said. “If you have many fat cells, the insulin is spread across many cells and the impact is diluted. But if you have no new fat cells being formed, the same cells are exposed to more and more insulin over and over, resulting in adipose inflammation and ultimately insulin resistance.

“So if you have too many Aregs, it may increase your chances of developing diabetes faster,” he continued. “We don’t know yet whether this actually holds true because we simply don’t understand the dynamics of it yet. The more we study single adipose cells, the more we learn that adipose is much more than a type of tissue you sit on.”