Shi 2023 Redox Biol

From Bioblast
Publications in the MiPMap
Shi L, Tao Z, Zheng L, Yang J, Hu X, Scott K, de Kloet A, Krause E, Collins JF, Cheng Z (2023) FoxO1 regulates adipose transdifferentiation and iron influx by mediating TgfΞ²1 signaling pathway.

Β» Redox Biol 63:102727. PMID: 37156218 Open Access

Shi Limin, Tao Zhipeng, Zheng Louise, Yang Jinying, Hu Xinran, Scott Karen, de Kloet Annette, Krause Eric, Collins James F, Cheng Zhiyong (2023) Redox Biol

Abstract: Adipose plasticity is critical for metabolic homeostasis. Adipocyte transdifferentiation plays an important role in adipose plasticity, but the molecular mechanism of transdifferentiation remains incompletely understood. Here we show that the transcription factor FoxO1 regulates adipose transdifferentiation by mediating TgfΞ²1 signaling pathway. TgfΞ²1 treatment induced whitening phenotype in beige adipocytes, reducing UCP1 and mitochondrial capacity and enlarging lipid droplets. Deletion of adipose FoxO1 (adO1KO) dampened TgfΞ²1 signaling by downregulating Tgfbr2 and Smad3 and induced browning of adipose tissue in mice, increasing UCP1 and mitochondrial content and activating metabolic pathways. Silencing FoxO1 also abolished the whitening effect of TgfΞ²1 on beige adipocytes. The adO1KO mice exhibited a significantly higher energy expenditure, lower fat mass, and smaller adipocytes than the control mice. The browning phenotype in adO1KO mice was associated with an increased iron content in adipose tissue, concurrent with upregulation of proteins that facilitate iron uptake (DMT1 and TfR1) and iron import into mitochondria (Mfrn1). Analysis of hepatic and serum iron along with hepatic iron-regulatory proteins (ferritin and ferroportin) in the adO1KO mice revealed an adipose tissue-liver crosstalk that meets the increased iron requirement for adipose browning. The FoxO1-TgfΞ²1 signaling cascade also underlay adipose browning induced by Ξ²3-AR agonist CL316243. Our study provides the first evidence of a FoxO1-TgfΞ²1 axis in the regulation of adipose browning-whitening transdifferentiation and iron influx, which sheds light on the compromised adipose plasticity in conditions of dysregulated FoxO1 and TgfΞ²1 signaling.

β€’ Bioblast editor: Plangger M

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Fat  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway:HRR: Oxygraph-2k 


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