The Capability to Undergo ACSL4-Mediated Ferroptosis Is Acquired During Brown-like Adipogenesis and Affected by Hypoxia.

ABSTRACT: Adipose tissue enlargement in obesity leads to hypoxia, which may promote premature aging. This study aimed to understand the hypoxic response in 3D cultures of SGBS cells, a model for brown-like adipose tissue expressing uncoupling protein 1 (UCP1). Single-nucleus RNA sequencing of SGBS organoids revealed a heterogeneous composition and sub-population-specific responses to hypoxia. The analysis identified a cluster of transcriptional repression, indicating dying cells, and implied a role of ferroptosis in this model. Further experiments with SGBS cells and white adipose tissue-derived stem/progenitor cells showed that Acyl-CoA synthetase long-chain family member 4 (ACSL4), a key enzyme in ferroptosis, is expressed only in the presence of browning factors. Hypoxia downregulated ACSL4 prote

SUBMITTER: Mandl M 

PROVIDER: S-EPMC12384742 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature