Adipose circular RNAs exhibit dynamic regulation in obesity and functional role in adipogenesis

Camille Arcinas, Wilson Tan, Wenning Fang, Tresha P. Desai, Diana Chee Siang Teh, Ufuk Degirmenci, Dan Xu, Roger Foo, Lei Sun

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Non-coding RNAs are emerging as novel regulators in adipocyte differentiation and function. Circular RNAs (circRNAs) are a new class of non-coding transcripts generated across all eukaryotic tissues, but their function in adipose biology remains unknown. Here we perform deep sequencing of visceral and subcutaneous fat to discover thousands of adipose circRNAs, many of which are species conserved, tissue specific and dynamically regulated during adipogenesis and obesity. We identify circTshz2-1 and circArhgap5-2 as indispensable regulators of adipogenesis in vitro. To characterize the function of circRNAs in vivo, we deliver adenoviral shRNA targeting circArhgap5-2 into mouse inguinal tissue and show that the expression of this circRNA is essential in maintaining the global adipocyte transcriptional programme involved in lipid biosynthesis and metabolism. We also demonstrate that the pro-adipogenic function of circArhgap5-2 is conserved in human adipocytes. Our results provide important evidence that circRNAs serve as important regulators in adipocyte differentiation and metabolism.

Original languageEnglish (US)
Pages (from-to)688-703
Number of pages16
JournalNature Metabolism
Volume1
Issue number7
DOIs
StatePublished - Jul 1 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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