Scientists identified cell populations that could be key to treating obesity

New cells discovered in human omental adipose tissue inhibit fat cell formation.

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Understanding fat tissue formation and function is significant for treating obesity and related metabolic diseases. However, adipose tissue, or body fat, behaves differently depending on where it is located in the body.

Consider the omentum, a substantial apron-like fatty tissue that hangs from the stomach and covers the stomach and intestines, among other organs located within the peritoneum. In addition to storing fat, it aids tissue repair and immunological control.

The “apple” body form is linked to omental adipose tissue and occurs when this fat depot grows dramatically, raising the risk of metabolic illnesses. This expansion is primarily the result of existing fat cells growing more extensive, a process known as hypertrophy, rather than new fat cells forming, a process known as adipogenesis. Insulin resistance and persistent inflammation may result from this.

In contrast to subcutaneous fat, omental fat has a restricted ability to produce new fat cells, a fact that is still poorly understood. Researchers at EPFL, under the direction of Professor Bart Deplancke, have now discovered a cell population in human omental adipose tissue that prevents adipogenesis. The finding, reported in Cell Metabolism, offers a fresh perspective on the restricted capacity of adipose tissue to carry out adipogenesis and has significant ramifications for managing obesity.

Using advanced single-cell RNA sequencing, scientists analyzed cells from various human fat depots, isolating different cellular subpopulations and testing their ability to turn into new fat cells.

The method found a cell population in the omental adipose tissue that could be crucial in understanding its peculiar characteristics. These cells, known as mesothelial cells, typically act as a protective layer lining specific internal body cavities.

A subset of these mesothelial cells underwent an odd transition toward mesenchymal cells, which can differentiate into adipocytes (fat cells), among other cell types. These cells’ ability to alter the omental adipose tissue’s adipogenic potential may largely depend on this dynamic shift between cellular states.

According to the study, these cells’ mesenchymal-like characteristics are linked to an improved capacity to control their microenvironment, offering a regulatory mechanism for restricting adipose tissue growth. Thus, by alternating between these two states, the cells could affect the omental fat depot’s overall metabolic behavior and its ability to store fat without leading to metabolic problems.

Radiana Ferrero (EPFL), one of the study’s lead authors, said, “Importantly, we also uncovered at least part of the molecular mechanism by which this new omental cell population affects adipogenesis. Specifically, the cells express high levels of Insulin-like Growth Factor Binding Protein 2 [IGFBP2], a protein known to inhibit adipogenesis and secrete this protein in the cells’ microenvironment. This, in turn, affects specific receptors on nearby adipose stem and progenitor cells, effectively preventing them from developing into mature fat cells.”

Pernille Rainer (EPFL), another lead researcher, said“The findings have deep implications for understanding and potentially managing metabolically unhealthy obesity. Knowing that omental fat has a built-in mechanism to limit fat cell formation could lead to new treatments that modulate this natural process. Furthermore, the research opens up possibilities for targeted therapies that could modulate the behavior of specific fat depots.”

Journal Reference:

  1. Radiana Ferrero, Pernille Yde Rainer, Marie Rumpler, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Nathalie Vionnet, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Kai-Uwe Schlaudraff, Carles Canto, and Bart Deplancke. A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion. Cell Metabolism 09 May 2024. DOI: 10.1016/j.cmet.2024.04.017

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