Peter Andreas, Schleicher Erwin, Kliemank Elisabeth, Szendroedi Julia, Königsrainer Alfred, Häring Hans-Ulrich, Nawroth Peter P, Fleming Thomas
German Centre for Diabetes Research (DZD), Helmholtz Centre Munich, 85764 Munich, Germany.
Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72016 Tübingen, Germany.
Metabolites. 2024 Apr 7;14(4):209. doi: 10.3390/metabo14040209.
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/m). 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.
非酒精性脂肪肝（NAFL）的发生及其向晚期肝病进展的潜在分子机制仍不清楚。乙二醛酶1（Glo1）缺失会导致甲基乙二醛（MG）升高和二羰基应激，这与包括肥胖相关疾病在内的多种疾病有关。本研究旨在调查非病理性肝脏脂肪个体中乙二醛酶系统的变化。从30名BMI范围较窄（24.6 - 29.8 kg/m）的个体获取肝脏活检样本。使用HOMA-IR评估全身胰岛素敏感性。对肝脏活检样本分析总甘油三酯含量、Glo1和Glo2 mRNA、蛋白质表达及活性。液相色谱 - 串联质谱法测定肝脏二羰基含量以及氧化和糖基化生物标志物。肝脏Glo1活性与HOMA-IR和肝脏甘油三酯含量呈负相关，但与BMI无关。尽管Glo1活性降低，但未发现与肝脏二羰基或糖基化标志物升高有关。在Glo1方面观察到性别差异，与男性相比，女性肝脏Glo蛋白表达和活性显著降低，肝脏MG-H1含量更高。本研究表明，即使在非病理性范围内，肝脏脂肪增加也与Glo1活性降低有关。
