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: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
7 April 2024
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| 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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| 520 | |a 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. | ||
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