Interleukin (IL)-15 is an important regulator of adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). This study was designed to clarify the underlying mechanism. BMSCs were obtained from Nanyang cattle and stimulated to differentiate into adipocytes using standard differentiation medium. Oil Red O staining was used to assess lipid accumulation. Western blotting and quantitative real-time polymerase chain reaction were used to assess protein and mRNA levels, respectively. Recombinant IL-15 treatment inhibited adipogenic differentiation of cattle BMSCs in vitro, as evidenced by reduced induction of the adipocyte markers, peroxisome proliferator activated receptor gamma (PPAR gamma) and fatty acid binding protein 4 (alpha P2). IL-15 not only activated the signal transducers and activators of transcription (STAT) pathway, but also attenuated the activation of phosphoinositide 3-kinase (PI3K)/Akt signalling by insulin, a major inducer of adipocyte differentiation. In the presence of the STAT-specific inhibitor, 573108, the inhibitory effect of IL-15 on PPAR gamma and alpha P2 expression was abolished. Meanwhile, IL-15-attenuated PI3K/Akt signalling was also rescued. IL-15 may regulate adipogenic differentiation of BMSCs by inhibiting PI3K/Akt activation via the STATSA pathway. Our data raise the possibility of using IL-15 in the therapy of obesity-related diseases, such as cardiovascular diseases and type 2 diabetes. (C) 2019 Elsevier Inc. All rights reserved.