Int J Biol Macromol. 2024 Feb;257(Pt 2):128613.doi: 10.1016/j.ijbiomac.2023.128613. Epub 2023 Dec 8.

Functionally conserved PPARG exonic circRNAs enhance intramuscular fat deposition by regulating PPARG and HSL

Affiliations

Affiliations

  • 1 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, Guangxi 530005, China.
  • 2 Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan, Guangdong 528225, China.
  • 3 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, Guangxi 530005, China. Electronic address: ardsshi@gxu.edu.cn.
  • 4 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, Guangxi 530005, China. Electronic address: huangjieping@gxu.edu.cn.

Abstract

Circular RNAs (circRNA) are a kind of endogenous biological macromolecules that play significant roles in many biological processes, including adipogenesis, a precisely orchestrated process that is mediated by a large number of factors. Among them, peroxisome proliferator-activated receptor gamma (PPARG), is undoubtedly the most important regulator of adipocyte development in all types of adipose tissue. The formation of intramuscular fat (IMF), is a key factor that influences the meat quality in livestock animals. PPARG has been demonstrated to show a positive correlation with IMF deposition although the regulatory mechanism involved is not known. This study demonstrates that PPARG mediates IMF deposition by producing multiple exonic circRNAs (circPPARGs). Three circPPARGs promote adipogenic differentiation and inhibit the proliferation of intramuscular preadipocytes and these effects are conserved across several species including buffaloes, cattle and mice. Notably, circPPARG1 interacts with PPARG protein to inhibit the transcription of hormone sensitive lipase (HSL) involved in lipolysis. In addition, the positive effects of circPPARG1 on IMF deposition were identified in mice in vivo. Thus, PPARG drives IMF deposition, not only through the common transcription factor pathway, but also by producing circRNAs. This study provides new insights into our understanding of the regulatory mechanisms of PPARG in IMF deposition.

Keywords: Adipogenesis; Bubalus bubalis; Intramuscular fat; Peroxisome proliferator-activated receptor gamma; circRNA.

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