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Monday, December 05, 2022

Increased levels of blood fats are more harmful than previously thought

Elevated levels of fat in the blood put pressure on muscle cells in patients with metabolic diseases. A new study shows that these stressed cells give off a signal called ceramides that can be delivered to other cells.

These signals confer a protective advantage in the short term because they are part of a mechanism designed to reduce stress in the cell. But, in metabolic diseases, these signals can kill cells, making the disease even more severe.

Increased fat in the blood has long been associated with an increased risk of damage to tissues and organs, leading to the development of cardiovascular and metabolic diseases, including type 2 diabetes. Obesity can cause this condition. In 2016, more than 650 million adults aged 18 and older were obese.

Research supervisor Lee Roberts, Professor of Molecular Physiology and Metabolism at the University of Leeds School of Medicine, said: “While this research is at an early stage, our finding may form the basis for new treatments or therapeutic approaches to prevent the development of cardiovascular and metabolic diseases, such as diabetes, in obese people with high blood fat.”

The scientists replicated the blood fat levels seen in humans with metabolic disease by exposing skeletal muscle cells to a fatty acid called palmitate. By doing this the cells trigger the ceramide signal.

When these cells were mixed with others that had not previously been exposed to fat, the researchers found that they communicated with each other. While communicating, they transmit signals in packages called extracellular vesicles.

Scientists reproduced the experiment on human volunteers with metabolic diseases. Their study provides an entirely new angle on how we respond to stress, with important consequences for our understanding of some metabolic diseases, including obesity.

Roberts said, “This research gives us a new perspective on how stress develops in the cells of obese individuals and provides new avenues to consider in developing new treatments for metabolic diseases.”

“With obesity an ever-increasing epidemic, the burden of chronic disease such as type 2 diabetes necessitates new treatments. We hope our research results will open a new avenue for research to help address this growing concern.” “

Journal Reference:

  1. McNally, BD, Ashley, DF, Hanske, L. At al. Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum tension in skeletal muscle. Nat Commune 13, 1748 (2022). DOI: 10.1038/s41467-022-29363-9

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