Adipose tissue dysfunction in response to obesity: pursuing the role of me1

Dysfunctional adipose tissue in obesity is now recognized as a major driver of metabolic disorders, inflammation, and cardiovascular disease. The accumulation of visceral adipose tissue (VAT) in particular is strongly linked to inflammatory disease conditions while subcutaneous adipose tissue (SAT) is linked to the metabolic healthy obese phenotype. However, the cellular adaptations underlying dysfunctional VAT and preserved function in SAT in response to obesity remain to be determined. We recently assessed obesity-induced changes to the adipose transcriptome in a mouse model of diet-induced obesity using RNA sequencing and revealed a small subset of genes that were differentially expressed in VAT vs. SAT relative to lean counterparts. Of these genes, me1 stood out based on its roles in cellular metabolism and redox regulation. The expression of me1, confirmed at the protein level using Western immunoblotting, was shown to be upregulated in SAT and downregulated in VAT of obese mice leading to our overarching hypothesis that differential regulation of me1 expression in adipose tissue may drive two indicators of VAT dysfunction, namely i) an increase in reactive oxygen species (ROS) and ii) blunted metabolic efficiency. In the present study, we determined if these indicators linked to me1 are differentially influenced in VAT and SAT of obese mice to establish a rationale for targeting me1 in future studies. First, ROS was directly measured using flow cytometry on single cell populations of digested adipose tissue stained with H2DCFDA as well as in lysed tissue using hydroethidine. Next, the NADP/NADPH ratio, governed in part by me1, was determined in VAT and SAT to assess obesity-induced changes to redox coupling and metabolism. While neither direct measure of ROS revealed significant differences, NADP/NADPH was highest in VAT from obese mice suggesting a decrease in NADP substrate utilization relative to lean controls and SAT from obese mice, which exhibited the lowest ratio. These findings in particular are in line with the expression profile of me1 in VAT vs. SAT of obese mice and suggest differences in metabolic efficiency in distinct adipose tissue challenged by obesity. These data support a rationale for studies catered to determining if increasing me1 expression restores the VAT NADP/NADPH ratio in obesity. National Institute of General Medical Sciences of the National Institutes of Health under award number 2P20GM113125 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.