How sugar promotes inflammation

Date:
March 22, 2022
Source:
University of Wu"rzburg
Summary:
Excessive sugar consumption can promote inflammatory processes in
the body and facilitate the development of autoimmune diseases. A
research team has now deciphered new details of these processes.



FULL STORY ========================================================================== People who consume sugar and other carbohydrates in excess over a
long period of time have an increased risk of developing an autoimmune
disease. In affected patients, the immune system attacks the body's own
tissue and the consequences are, for example, chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, type 1 diabetes
and chronic inflammation of the thyroid gland.


==========================================================================
New targets for therapy The underlying molecular mechanisms that promote autoimmune diseases are multilayered and complex. Now, scientists at
the Julius Maximilians University of Wu"rzburg (JMU) have succeeded in deciphering new details of these processes. Their work support the notion
that excessive consumption of glucose directly promotes the pathogenic functions of certain cells of the immune system and that, conversely,
that a calorie-reduced diet can have a beneficial effect on immune
diseases. Based on these findings, they also identified new targets
for therapeutic interventions: A specific blockade of glucose-depended metabolic processes in these immune cells can suppress excessive immune reactions.

Dr. Martin Va"th is responsible for the study, which has now been
published in the journal Cell Metabolism. He is a junior research group
leader at the Institute of Systems Immunology -- a Max Planck research
group under the umbrella of JMU that focusses on the interplay of the
immune system with the organism. Collaborators from Amsterdam, Berlin,
Freiburg and Leuven were also involved in this study.

Glucose transporter with a side job Martin Va"th explains: "Immune cells
need large amounts of sugar in the form of glucose to perform their
tasks. With the help of specialized transporters at their cell membrane,
they can take up glucose from the environment." Together with his team,
Va"th has showed that a specific glucose transporter - - scientifically
named GLUT3 -- fulfills additional metabolic functions in T cells besides
the generating energy from sugar.

In their study, the scientists focused on a group of cells of the immune
system that have not been known for very long: T helper cells of type 17,
also called Th17 lymphocytes, which play an important role in regulating
(auto- ) inflammatory processes.

"These Th17 cells express lots of GLUT3 protein on their cell surface,"
Va"th explains. Once taken up, glucose is readily converted to citric
acid in the mitochondria before it is metabolized into acetyl-coenzyme
A (acetyl-CoA) in the cytoplasm. Acetyl-CoA is involved in numerous
metabolic processes, including the biosynthesis of lipids.

Influence on proinflammatory genes However, acetyl-CoA fulfills additional functions in inflammatory Th17 cells.

Va"th and his team showed that this metabolic intermediate can also
regulate the activity of various gene segments. Thus, glucose consumption
has a direct influence on the activity of proinflammatory genes.

According to the researchers, theses new findings pave the way for the development of targeted therapy of autoimmune diseases. For example,
blocking GLUT3-dependent synthesis of acetyl-CoA by the dietary supplement hydroxycitrate, which is used to treat obesity, can mitigate the
pathogenic functions of Th17 cells and reduce inflammatory-pathological processes. The so- called "metabolic reprogramming" of T cells opens new possibilities to treat autoimmune diseases without curtailing protective
immune cell functions.


========================================================================== Story Source: Materials provided by University_of_Wu"rzburg. Original
written by Gunnar Bartsch. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Sophia M. Hochrein, Hao Wu, Miriam Eckstein, Laura Arrigoni,
Josip S.

Herman, Fabian Schumacher, Christian Gerecke, Mathias Rosenfeldt,
Dominic Gru"n, Burkhard Kleuser, Georg Gasteiger, Wolfgang
Kastenmu"ller, Bart Ghesquie`re, Jan Van den Bossche, E. Dale Abel,
Martin Vaeth. The glucose transporter GLUT3 controls T helper 17
cell responses through glycolytic- epigenetic reprogramming. Cell
Metabolism, 2022; DOI: 10.1016/ j.cmet.2022.02.015 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220322122836.htm

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