Chronic, systemic inflammation is a major pathophysiological manifestation of obesity and contributes to the development of metabolic disorders, including insulin resistance. Inflammatory signaling leads to elevated glycolytic flux and a metabolic shift towards aerobic glycolysis. This increase in glycolytic flux, in turn, leads to an increase in glycolytic byproducts. One such product, methylglyoxal, is detoxified by the glyoxalase cycle, which is comprised of two enzymes, glyoxalase 1 (GLO1) and 2 (GLO2). Using CRISPR-Cas9 we knocked out either GLO1 or GLO2 from RAW264.7 mouse macrophages. We found the glyoxalase intermediate lactoylglutathione (LGSH) plays a critical role in the inflammatory response during pathophysiologically relevant scenarios where glycolytic flux is elevated. When GLO1 is knocked out, LGSH is reduced, along with the inflammatory response. In contrast, when GLO2 is knocked out, LGSH and RAW264.7 macrophage inflammatory response is elevated. Collectively, this data contributes to the elucidation of regulatory mechanisms involved in the response to inflammation.

Regulatory role of the glyoxalase cycle in inflammation

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.