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Mesothelial cells in omental adipose tissue hinder adipogenesis

Posted: 13 May 2024 | | No comments yet

The discovery that omental fat has a mechanism to limit adipocyte formation may lead to new treatments for obesity and metabolic disease.

adipose

Researchers at EPFL have identified a population of cells in human omental adipose tissue that hinders adipogenesis. This finding has significant implications for obesity management.

To address obesity and related metabolic diseases, understanding how fat tissue forms and functions is essential. However, adipose tissue behaves differently based on its location in the body. For example, the omentum, a fatty tissue hanging from the stomach that covers organs within the peritoneum, stores fat, yet also plays parts in immune regulation and tissue regeneration. Omental adipose tissue emerges when this fat depot expands, elevating the risk of metabolic diseases. This expansion is mostly due to the enlargement of existing fat cells, a process named hypertrophy, instead of the formation of new fat cells (adipogenesis). Hypertrophy can lead to chronic inflammation and insulin resistance.

Led by Dr Bart Deplancke, the team used advanced single-cell RNA sequencing to analyse cells from various human fat depots, isolating different cellular subpopulations and assessing their ability to turn into new fat cells. Supported by multiple medical institutions including the CHUV, this study involved over thirty human donors to enable a detailed comparison across different fat locations.

The approach found a population of cells, called mesothelial cells, present in the omental adipose tissue that could be key for elucidating its unusual properties. Among these mesothelial cells, some transitioned closer to mesenchymal cells, which can develop into a variety of cell types including adipocytes. The transition between cellular states could be a mechanism through which these cells exert their influence on the adipogenic potential of the omental adipose tissue.

An enhanced ability to modulate their microenvironment is associated with the mesenchymal-like properties of these cells, provide a mechanism for reducing the expansion of adipose tissue. By switching between these two states, the cells may be able to influence the overall metabolic behaviour of the omental fat depot and its capacity to accumulate fat without triggering metabolic complications.

One of the study’s lead authors Dr Radiana Ferrero commented: “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.”

“The findings have deep implications for understanding and potentially managing metabolically unhealthy obesity,” concluded Dr Pernille Rainer, another lead researcher on the study. “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 behaviour of specific fat depots.”

This study was published in Cell Metabolism.

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