Obesity is often accompanied by metabolic changes in adipocytes that are closely associated with metabolic disease. Although high sugar consumption contributes to obesity, it may also directly affect adipocytes by increasing the rate of glycolysis and formation of the glycolytic by-product methylglyoxal (MG). MG is a reactive dicarbonyl that irreversibly damages proteins and other cellular components. Although the accumulation of MG is clinically associated with hyperglycemia and diabetic complications, a better understanding of how proteins are regulated by MG is needed to evaluate its role in the pathogenesis of metabolic disease. Because adipocytes rely heavily on glycolysis for glucose disposal, we hypothesized that prolonged MG treatment at nontoxic concentrations would impact the landscape of proteins involved in glucose metabolism. To test this hypothesis, we treated 3T3-L1 adipocytes with MG (100 μmol/L) and used comparative proteomics to assess the effects. We identified 25 differentially expressed proteins in adipocytes treated with MG compared to the control. Our results suggested that MG induced metabolic changes typically associated with aerobic glycolysis, including a lowered expression of proteins involved in oxidative metabolism and increased expression of the glycolytic enzymes L-lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The detection of increased lactate secreted into the culture media of adipocytes treated with MG further supported these findings, as did gene expression analysis. In summary, these results indicate MG as a metabolic contributor to aerobic glycolysis in adipocytes, a potential adaptive response to increased glucose flux which over time could lead to permanent metabolic changes.

中文翻译：

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有氧糖酵解作为脂肪细胞中甲基乙二醛的潜在代谢靶点的蛋白质组学鉴定

肥胖往往伴随着脂肪细胞的代谢变化，这些变化与代谢疾病密切相关。尽管高糖消耗会导致肥胖，但它也可能通过增加糖酵解速率和糖酵解副产物甲基乙二醛 (MG) 的形成直接影响脂肪细胞。MG 是一种反应性二羰基化合物，可不可逆地破坏蛋白质和其他细胞成分。尽管 MG 的积累在临床上与高血糖和糖尿病并发症有关，但需要更好地了解 MG 如何调节蛋白质以评估其在代谢疾病发病机制中的作用。由于脂肪细胞严重依赖糖酵解进行葡萄糖处理，我们假设在无毒浓度下长期 MG 治疗会影响参与葡萄糖代谢的蛋白质的景观。为了验证这一假设，我们用 MG (100 μmol/L) 处理 3T3-L1 脂肪细胞，并使用比较蛋白质组学来评估效果。与对照相比，我们在用 MG 处理的脂肪细胞中鉴定了 25 种差异表达的蛋白质。我们的结果表明，MG 诱导的代谢变化通常与有氧糖酵解相关，包括参与氧化代谢的蛋白质表达降低和糖酵解酶 L-乳酸脱氢酶和 3-磷酸甘油醛脱氢酶的表达增加。检测到分泌到用 MG 处理的脂肪细胞培养基中的乳酸增加，进一步支持了这些发现，基因表达分析也是如此。总之，这些结果表明 MG 作为脂肪细胞有氧糖酵解的代谢贡献者，