Obesity prevalence in the US has nearly tripled since 1975 and a parallel increase in prevalence of type 2 diabetes (T2D). Obesity promotes a myriad of metabolic derangements with insulin resistance (IR) being perhaps the most responsible for the development of T2D and other related diseases such as cardiovascular disease. The precarious nature of IR development is such that it provides a valuable target for the prevention of further disease development. However, the mechanisms driving IR are numerous and complex making the development of viable interventions difficult. The development of metabolic derangement in the context of obesity promotes accumulation of reactive metabolites such as the reactive alpha-dicarbonyl methylglyoxal (MG). MG accumulation has long been appreciated as a marker of disease progression in patients with T2D as well as the development of diabetic complications. However, recent evidence suggests that the accumulation of MG occurs with obesity prior to T2D onset and may be a primary driving factor for the development of IR and T2D. Further, emerging evidence also suggests that this accumulation of MG with obesity may be a result in a loss of MG detoxifying capacity of glyoxalase I. In this review, we will discuss the evidence that posits MG accumulation because of GLO1 attenuation is a novel target mechanism of the development of metabolic derangement. In addition, we will also explore the regulation of GLO1 and the strategies that have been investigated so far to target GLO1 regulation for the prevention and treatment of metabolic derangement.

自 1975 年以来，美国的肥胖患病率几乎增加了两倍，2 型糖尿病(T2D) 的患病率也相应增加。肥胖会导致多种代谢紊乱，其中胰岛素抵抗 (IR) 可能是导致 T2D 和心血管疾病等其他相关疾病的最主要原因。IR 发展的不稳定性质使其为预防疾病进一步发展提供了有价值的目标。然而，驱动 IR 的机制众多且复杂，使得制定可行的干预措施变得困难。肥胖背景下代谢紊乱的发展会促进反应性代谢物的积累，例如反应性α-二羰基甲基乙二醛（MG）。长期以来，MG 积累一直被认为是 T2D 患者疾病进展以及糖尿病并发症发生的标志。然而，最近的证据表明，MG 的积累在 T2D 发病前随肥胖发生，可能是 IR 和 T2D 发展的主要驱动因素。此外，新出现的证据还表明，肥胖引起的 MG 积累可能是乙二醛酶 I MG 解毒能力丧失的结果。在这篇综述中，我们将讨论由于 GLO1 减弱而导致 MG 积累是一种新的靶机制的证据。代谢紊乱的发展。此外，我们还将探讨GLO1的调控以及迄今为止已研究的针对GLO1调控以预防和治疗代谢紊乱的策略。