FoxO1 regulates adipose transdifferentiation and iron influx by mediating Tgfβ1 signaling pathway

• DOI: 10.1016/j.redox.2023.102727
• Publication Date: 2023-05-02T21:21:55Z
• Authors: Limin Shi; Zhipeng Tao; Louise Zheng; Jinying Yang; Xinran Hu; Karen Scott; Annette de Kloet; Eric Krause; James F. Collins; Zhiyong Cheng
• Keywords: Transdifferentiation; Thermogenin; PRDM16; FOXO1; Adipose tissue macrophages

Adipose plasticity is critical for metabolic homeostasis. Adipocyte transdifferentiation plays an important role in adipose plasticity, but the molecular mechanism of remains incompletely understood. Here we show that transcription factor FoxO1 regulates by mediating Tgfβ1 signaling pathway. treatment induced whitening phenotype beige adipocytes, reducing UCP1 and mitochondrial capacity enlarging lipid droplets. Deletion (adO1KO) dampened downregulating Tgfbr2 Smad3 browning tissue mice, increasing content activating pathways. Silencing also abolished effect on adipocytes. The adO1KO mice exhibited a significantly higher energy expenditure, lower fat mass, smaller adipocytes than control mice. was associated with increased iron tissue, concurrent upregulation proteins facilitate uptake (DMT1 TfR1) import into mitochondria (Mfrn1). Analysis hepatic serum along iron-regulatory (ferritin ferroportin) revealed tissue-liver crosstalk meets requirement browning. FoxO1-Tgfβ1 cascade underlay β3-AR agonist CL316243. Our study provides first evidence axis regulation browning-whitening influx, which sheds light compromised conditions dysregulated signaling.