# Glyoxalase 1 is a proadipogenic gene

## TL;DR

This study shows that the enzyme GLO1 supports fat cell development, suggesting it plays a key role in obesity and diabetes.

## Contribution

The study identifies GLO1 as a proadipogenic gene through experiments with knockout cells.

## Key findings

- GLO1 knockout cells fail to accumulate lipid during adipogenesis despite high MGO levels.
- GLO1−/− cells show reduced AKT phosphorylation and glucose uptake after differentiation.
- Proteomic analysis reveals fewer glycolytic enzymes in GLO1−/− cells compared to wild-type cells.

## Abstract

Diabetes is one of the most prevalent and widespread diseases, with the majority of cases stemming from prolonged obesity. Obesity occurs through the expansion of adipose tissue in an unhealthy and dysfunctional manner, where patients develop inflammation and insulin resistance. Diabetic patients have increased levels of the reactive glycolytic byproduct, methylglyoxal (MGO), and its resulting post-translational modifications (PTMs) compared with nondiabetic patients. To combat this, cells are equipped with the glyoxalase cycle, consisting of two enzymes, glyoxalase 1 (GLO1) and GLO2, to reduce the levels of MGO. Previous work has identified a putative role for MGO in the pathologies associated with obesity. We thus sought to interrogate the role of GLO1 in the context of adipogenesis using GLO1 knockout (GLO1−/−) 3T3-L1 preadipocytes. These cells have elevated, physiologically relevant, levels of MGO and MGO-derived PTMs. When differentiated to mature adipocytes, GLO1−/− cells fail to accumulate lipid, despite significant elevations in MGO. We also show a restoration of MGO-derived PTMs in GLO1−/− cells following differentiation. Proteomic analysis reveals significant enrichment in glycolytic and tricarboxylic acid cycle enzymes in WT cells compared with GLO1−/− cells after differentiation. Last, immunoblotting shows decreased AKT phosphorylation and reduced glucose uptake in differentiated GLO1−/− cells. Taken together, our data identify a putative proadipogenic role for GLO1 and MGO in adipogenesis.