E4BP4 Safeguards Brown Fat Mitochondria from Obesity-Induced Fragmentation via Ceramide Repression

ABSTRACT: Brown adipose tissue (BAT) counteracts obesity-related metabolic dysfunction through both thermogenic and non-thermogenic means. However, substantial evidence indicates that obesity negatively affects BAT mitochondrial morphology and oxidative capacity, impairing systemic energy homeostasis. Motivated by this apparent contradiction, we investigate the relationship between obesity and mitochondrial dynamics, as the underlying mechanisms remain incompletely understood. Here, we identify E4BP4 as a transcriptional repressor that prevents obesity-induced mitochondrial fragmentation and oxidative dysfunction by inhibiting ceramide synthesis in brown fat. Specifically, E4BP4 interacts with PRDM16 to repress Cers6 mRNA expression and consequently reduces C16:0 ceramide levels by binding to a 65 k

SUBMITTER: Carlos, Henrique Sponton 

PROVIDER: S-SCDT-10_1038-S44319-026-00826-0 | biostudies-other |

REPOSITORIES: biostudies-other