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Accumulation of non-pathological liver fat is associated with the loss of glyoxalase I activity in humans

The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesit...

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Main Authors: Peter, Andreas (Author) , Schleicher, Erwin (Author) , Kliemank, Elisabeth (Author) , Szendrödi, Julia (Author) , Königsrainer, Alfred (Author) , Häring, Hans-Ulrich (Author) , Nawroth, Peter Paul (Author) , Fleming, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 7 April 2024
In: Metabolites
Year: 2024, Volume: 14, Issue: 4, Pages: 209-1-209-13
ISSN:2218-1989
DOI:10.3390/metabo14040209
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/metabo14040209
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2218-1989/14/4/209
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Author Notes:Andreas Peter, Erwin Schleicher, Elisabeth Kliemank, Julia Szendroedi, Alfred Königsrainer, Hans-Ulrich Häring, Peter P. Nawroth and Thomas Fleming
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Summary:The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed to investigate changes in the glyoxalase system in individuals with non-pathological liver fat. Liver biopsies were obtained from 30 individuals with a narrow range of BMI (24.6-29.8 kg/m2). Whole-body insulin sensitivity was assessed using HOMA-IR. Liver biopsies were analyzed for total triglyceride content, Glo1 and Glo2 mRNA, protein expression, and activity. Liquid chromatography-tandem mass spectrometry determined liver dicarbonyl content and oxidation and glycation biomarkers. Liver Glo1 activity showed an inverse correlation with HOMA-IR and liver triglyceride content, but not BMI. Despite reduced Glo1 activity, no associations were found with elevated liver dicarbonyls or glycation markers. A sex dimorphism was observed in Glo1, with females exhibiting significantly lower liver Glo1 protein expression and activity, and higher liver MG-H1 content compared to males. This study demonstrates that increasing liver fat, even within a non-pathological range, is associated with reduced Glo1 activity.
Item Description:Gesehen am 11.11.2024
Physical Description:Online Resource
ISSN:2218-1989
DOI:10.3390/metabo14040209

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