CircGLIS3 Regulates the Proliferation and Apoptosis of Bovine Intramuscular Preadipocytes via the miR-21-3p/PDPK1/AKT Axis

Adipogenesis, a complex process, is primarily determined by the number of preadipocytes and their adipogenic capacity. Preadipocyte proliferation and apoptosis regulate this cellular reserve, which is essential for adipogenic differentiation. CircRNAs are significant regulators of various cellular processes, yet their roles in preadipocyte proliferation and apoptosis remain underexplored. In this study, gain- and loss-of-function experiments show that circGLIS3 promotes proliferation and restrains the apoptosis of bovine intramuscular preadipocytes. Mechanistically, circGLIS3 serves as a molecular sponge for miR-21-3p, thereby derepressing PDPK1 and activating the Akt signaling pathway, as validated by dual-luciferase reporter, RNA immunoprecipitation, and rescue assays. Notably, circGLIS3 exhibits high sequence conservation between the <i>Bos taurus</i> and <i>Mus musculus</i>. In vivo overexpression of circGLIS3 in mouse skeletal muscle increased PDGFRα- and Pref-1-positive preadipocyte populations. This study elucidates the molecular mechanism by which the circGLIS3/miR-21-3p/PDPK1/Akt axis regulates bovine preadipocyte proliferation and apoptosis, thereby providing significant theoretical insights into bovine IMF deposition.