Adipose circular RNAs exhibit dynamic regulation in obesity and functional role in adipogenesis.
Arcinas Camille Esther WaletWilson TanWenning FangTresha P DesaiDiana Chee Siang TehUfuk DegirmenciDan XuRoger Sik Yin FooLei SunPublished in: Nature metabolism (2019)
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.
Keyphrases
- insulin resistance
- adipose tissue
- high fat diet induced
- transcription factor
- metabolic syndrome
- fatty acid
- skeletal muscle
- type diabetes
- gene expression
- poor prognosis
- weight loss
- endothelial cells
- randomized controlled trial
- weight gain
- long non coding rna
- prostate cancer
- clinical trial
- heat shock
- drug delivery
- study protocol
- heat shock protein
- pluripotent stem cells