Identifying Ferroptosis-Related Genes Associated with Weight Loss Outcomes and Regulation of Adipocyte Microenvironment.

ABSTRACT

SCOPE The study is about the influence of ferroptosis-related genes combined with the immune microenvironment exerted on weight control outcomes and systematic analysis. METHODS AND RESULTS: Subcutaneous adipose tissue (sWAT) samples from 11 subjects with good outcome and 10 subjects with poor outcome in weight management are obtained from the Gene Expression Omnibus database. The results are validated in vivo in animal models with different weight loss outcomes. The CIBERSORT algorithm is used to evaluate the differences in immune cell infiltration in each sample. Patients with poor outcome have higher levels of ferroptosis in the adipose tissue. Remarkable differences in cytokine production, nuclear factor kappa-B(NF-κB) transcription factor activity, leukocyte migration involved in the inflammatory response, and other biological processes are also observed compared to that in the well-controlled group. Aldo-keto reductase family 1-member C1(AKR1C1), nuclear receptor coactivator 4(NCOA4), and glutamate-cysteine ligase catalytic subunit(GCLC) are identified as core predictive markers and their expression patterns are confirmed in animal models. CONCLUSIONS: Ferroptosis and its mediated inflammation play an important role in long-term weight control, and analyses of the role of ferroptosis-related genes(FRGs) in weight control may provide new potential therapeutic targets for long-term weight control. Anti-inflammatory diets that mitigate inflammatory responses and affect ferroptosis may be considered in the future to improve weight control.