Interleukin-4-induced FABP4 promotes lipogenesis in human skeletal muscle cells by activating the PPAR γ signaling pathway.

Chronic low back pain (CLBP) is a common symptom of lumbar degenerative disease. Degeneration of the lumbar paravertebral muscles causes a loss of muscle mass and strength, which is a vital factor causing CLBP and often accompanied by lipid infiltration. Tandem mass spectrometry (TMT) was used to identify differentially expressed proteins in lipid-infiltrated and normal muscles. The results show that fatty acid binding protein 4 (FABP4) participated in the peroxisome proliferator-activated receptor-γ (PPAR γ) signaling pathway as an up-regulated protein, which is related to lipogenesis in diverse cells. In addition, chronic inflammation is believed to be involved in lumbar muscle degeneration and lipogenesis, with interleukin-4 (IL-4) considered as the predominant contributor. In present study, we investigate the effect of FABP4 on lipogenesis in human skeletal muscle cells (HSMCs) stimulated by Interleukin-4 (IL-4) and explore the mechanistic basis. We found expression level of FABP4 in lipid-infiltrated muscles was significantly higher than that in normal muscles. Lipogenesis in HSMCs could be increased by IL-4 treatment, as well as by FABP4 overexpression. FABP4 inhibition suppressed IL-4-mediated lipogenesis in HSMCs, whereas the PPAR γ inhibitor alleviated lipogenesis in both IL-4-treated and FABP4-overexpressed HSMCs. Collectively, the results indicate that FABP4 induces lipogenesis in HSMCs stimulated with IL-4 via activating the PPAR γ signaling pathway. Our study offers a detailed perspective on the pathogenesis of muscle lipid infiltration and provides a potential target for the clinical treatment strategy of muscle lipid infiltration and CLBP.