On April 1, 2022, researchers from the University of Leeds School of Medicine highlighted some of the key points of their research in the journal Nature Communications, which warns of the dangers of high levels of fat in the bloodstream that contribute to "lipotoxicity" and that cause subsequent physiologic reactions from the signals these cells send to others in the body.

Research supervisor Lee Roberts, professor of molecular physiology and metabolism at the University of Leeds School of Medicine, and colleagues that included an international research team from the University of Cambridge, University of Bonn, University of Bari, and Imperial College, explored the impact of chronic stress in skeletal muscle, specifically on the endoplasmic reticulum (ER), which is known to regulate the biosynthesis of both lipids and cellular proteins.

Their work builds on previous research that links this stressed skeletal muscle to metabolic disease in patients with lipotoxicity. Type 2 diabetes and other metabolic diseases, including obesity, are associated with high concentrations of saturated fatty acids, especially with palmitate, which are believed to be responsible for metabolic dysfunction in insulin-sensitive tissue.

Although, the mechanisms linking palmitate with the induction of ER stress remain unclear, it is hypothesized that the signals, known as ceramides, may confer a protective benefit in the short term because they are part of a mechanism designed to reduce stress in the cell. But for long-term conditions, such as metabolic diseases, the signals can kill the cells and worsen the symptoms and prognosis of the illness itself.

The research team was able to replicate the elevated fat observed in subjects with metabolic disease by exposing skeletal muscle cells to palmitate, which triggers them to begin sending the ceramide signal. The authors reported that "when these cells were mixed with others which had not been previously exposed to fats, the researchers found that they communicated with each other, transporting the signal in packages called extracellular vesicles."

According to Dr. Roberts, "Although this research is at an early stage, our discovery may form the basis of new therapies or therapeutic approaches to prevent the development of cardiovascular and metabolic diseases such as diabetes in people with elevated blood fats in obesity," He added, "This research gives us a novel perspective on how stress develops in the cells of individuals with obesity, and provides new pathways to consider when looking to develop new treatments for metabolic diseases. With obesity an ever-increasing epidemic, the burden of associated chronic disease such as type 2 diabetes necessitates new treatments. We hope the results of our research here open a new avenue for research to help address this growing concern."

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