Higher blood fats more harmful than first thought

Date:
April 1, 2022
Source:
University of Leeds
Summary:
The increased levels of blood fats in people with type 2 diabetes
and obesity are more harmful than previously thought, a new study
has found.

The research shows they can kill cells, make symptoms more severe,
and worsen the illness. 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.



FULL STORY ========================================================================== Increased levels of blood fats 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.

University of Leeds researchers have discovered 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.

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 since 1975. 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." 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.

Professor 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." The paper, titled 'Long-chain
ceramides are cell non-autonomous signals linking lipotoxicity to
endoplasmic reticulum stress in skeletal muscle', is published today in
Nature Communications.

The international research team included colleagues from the University of Cambridge, the University of Bonn, University of Bari, Imperial College
and AstraZeneca.


========================================================================== Story Source: Materials provided by University_of_Leeds. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Ben D. McNally, Dean F. Ashley, Lea Ha"nschke, He'le`ne N. Daou,
Nicole
T. Watt, Steven A. Murfitt, Amanda D. V. MacCannell, Anna
Whitehead, T.

Scott Bowen, Francis W. B. Sanders, Michele Vacca, Klaus
K. Witte, Graeme R. Davies, Reinhard Bauer, Julian L. Griffin,
Lee D. Roberts. Long-chain ceramides are cell non-autonomous
signals linking lipotoxicity to endoplasmic reticulum stress
in skeletal muscle. Nature Communications, 2022; 13 (1) DOI:
10.1038/s41467-022-29363-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220401094824.htm

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