Elevated fat levels in blood in patients with metabolic diseases stress the muscle cells. These stressed-out cells give off a signal known as ceramides that can be passed on to other cells, suggests a new study.
These signals offer protective benefits in the short term as they are part of a mechanism designed to reduce stress in the cell. But, in metabolic diseases, these signals can kill the cells, making the disease more severe.
Increased fat in blood has long been associated with the 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, there were more than 650 million adults aged 18 and above with obesity.
Research supervisor Lee Roberts, Professor of Molecular Physiology and Metabolism in the University of Leeds‘s School of Medicine, said: “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.”
Scientists replicated the blood fat levels observed in humans with metabolic disease by exposing skeletal muscle cells to a fatty acid called palmitate. Doing so causes the cells to trigger the ceramide signal.
When these cells were mixed with others that had not been previously exposed to fats, the researchers found that they communicated with each other. While communicating, they transmit the signal in packages called extracellular vesicles.
Scientists reproduced the experiment on human volunteers with metabolic diseases. Their study offers an entirely new angle on how cells respond to stress, with significant consequences for our understanding of certain metabolic diseases, including obesity.
Roberts said, “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.”
- McNally, B.D., Ashley, D.F., Hänschke, L. et al. Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle. Nat Commun 13, 1748 (2022). DOI: 10.1038/s41467-022-29363-9