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2024-02

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cc-by-nc-nd (c) Castellá Giner, Moisés et al., 2024
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/219694

The splicing factor SF3B1 is involved in brown adipocyte thermogenic activation

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https://doi.org/10.1016/j.bcp.2023.116014

Abstract

The ability of alternative splicing mechanisms to control gene expression is increasingly being recognized as relevant for adipose tissue function. The expression of SF3B1, a key component of the SF3B complex directly involved in spliceosome formation, was previously reported to be significantly induced in brown adipose tissue under cold-induced thermogenic activation. Here, we identify that noradrenergic cAMP-mediated thermogenic stimulation increases SF3B1 expression in brown and beige adipocytes. We further show that pladienolide-B, a drug that binds SF3B1 to inhibit pre-mRNA splicing by targeting the SF3B complex, down-regulates key components of the thermogenic machinery (e.g., UCP1 gene expression), differentially alters the expression of alternative splicing-regulated transcripts encoding molecular actors involved in the oxidative metabolism of brown adipocytes (e.g., peroxisome proliferator-activated receptor-gamma co-activator-alpha [PGC-1α] and cytochrome oxidase subunit 7a genes), and impairs the respiratory activity of brown adipocytes. Similar alterations were found in brown adipocytes with siRNA-mediated knockdown of SF3B1 protein levels. Our findings collectively indicate that SF3B1 is a key factor in the appropriate thermogenic activation of differentiated brown adipocytes. This work exemplifies the importance of splicing processes in adaptive thermogenesis and suggests that pharmacological tools, such as pladienolide-B, may be used to modulate brown adipocyte thermogenic activity.

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Teixit adipós, Obesitat, Expressió gènica

Subject (English)

Adipose tissues, Obesity, Gene expression

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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CASTELLÁ GINER, Moisés, et al. The splicing factor SF3B1 is involved in brown adipocyte thermogenic activation. Biochemical Pharmacology. 2024. Vol. 220, num. 1-11. ISSN 0006-2952. [consulted: 17 of August of 2026]. Available at: https://hdl.handle.net/2445/219694

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