London, April 3
Increased levels of blood fats, also known as lipids, in people with Type 2 diabetes and obesity are more harmful than previously thought, a new study has found.
In patients with metabolic diseases, elevated fat levels in the blood create stress in muscle cells — a reaction to changes outside the cell which damage their structure and function.
The study, published in the journal Nature Communications showed that these stressed-out cells give off a signal which can be passed on to other cells.
The signals, known as ceramides, may have a protective benefit in the short-term, because they are part of a mechanism designed to reduce stress in the cell. But in metabolic diseases, which are long term conditions, the signals can kill the cells, make symptoms more severe, and worsen the illness, said researchers at University of Leeds in the UK.
Increased fat in the blood has long been known to damage tissues and organs, contributing to the development of cardiovascular and metabolic diseases including Type 2 diabetes. The condition can be caused by obesity, rates of which have nearly tripled worldwide between 1975 and 2020.
"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," said Lee Roberts, Professor of Molecular Physiology and Metabolism in the University's School of Medicine.
"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," he added.
In the lab, the team replicated the blood fat levels observed in humans with metabolic disease by exposing skeletal muscle cells to a fatty acid called palmitate. The cells began to transmit the ceramide signal.
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.
The experiment was reproduced in human volunteers with metabolic diseases and gave comparable results. The findings provide a completely new angle on how cells respond to stress, with important consequences for our understanding of certain metabolic diseases including obesity.
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