Abstract
Intramuscular fat deposition or marbling is essential for high quality beef. The molecular mechanism of adipogenesis in skeletal muscle remains largely unknown. In this study, we isolated Platelet-derived growth factor receptor α (PDGFRα) positive progenitor cells from fetal bovine skeletal muscle and induced into adipocytes. Using miRNAome sequencing, we revealed that bta-miR-23a was an adipogenic miRNA mediating bovine adipogenesis in skeletal muscle. The expression of bta-miR-23a was down-regulated during differentiation of PDGFRα+ progenitor cells. Forced expression of bta-miR-23a mimics reduced lipid accumulation and inhibited the key adipogenic transcription factor peroxisome proliferative activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα). Whereas down-regulation of bta-miR-23a by its inhibitors increased lipid accumulation and expression of C/EBPα, PPARγ and fatty acid-binding protein 4 (FABP4). Target prediction analysis revealed that ZNF423 was a potential target of bta-miR-23a. Dual-luciferase reporter assay revealed that bta-miR-23a directly targeted the 3′-UTR of ZNF423. Together, our data showed that bta-miR-23a orchestrates early intramuscular adipogeneic commitment as an anti-adipogenic regulator which acts by targeting ZNF423.
Highlights
Protein 423 (ZNF423, known as ZFP423) was identified as another important regulator and involved in both adipogenic commitment of progenitor cells and PPARγ activation[13]
Satellite cells stay in quiescent, but have capacity to fuse with muscle fiber when they are activated[32], which is important for postnatal skeletal muscle growth[33] and skeletal muscle regeneration in adulthood[34,35]
Satellite cells derive from myogenic progenitor cells and do not have adipogenic potential[7]
Summary
Protein 423 (ZNF423, known as ZFP423) was identified as another important regulator and involved in both adipogenic commitment of progenitor cells and PPARγ activation[13]. Stromal vascular cells expressing ZNF423 have robust adipogenesis potential[14]. ZNF423 could promote adipogenic differentiation in bovine skeletal muscle derived stromal vascular cells[16]. Mature miRNAs interact with target mRNAs at specific sites of 3′untranslated regions (3′UTR) by base pairing. Being the key regulation factors, miRNAs play crucial roles in various biological process such as cell growth, differentiation and development. Since the important role in fetal development and its profound impact on IMF deposition, the objective of this study is to characterize the miRNAome expression profile during adipogenesis and determine their role in adipogenic differentiation of bovine progenitor cells. The significance of this study is to help understand how miRNA regulated intramuscular development during fetal stage in bovine
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