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

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Abstract

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.

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Acknowledgements

The authors would like to acknowledge the assistance of Dr. Chuan-dong Lang in the preparation of this article.

Author contributions

Conceived and designed the experiments: X.-W.W., Y.-J.S.; Performed the experiments: X.-W.W., Y.-J.S.; Statistical analysis: X.-W.W., X.C.; Wrote the paper: X.-W.W., Y.-J.S., W.-Z.Z. All authors read and approved the final manuscript.

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This research was supported by the Fundamental Research Funds for the Central Universities (WK9110000189).

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  1. Spine Center, Department of Orthopedics, Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, China

    Xin-wen Wang, Yong-jin Sun, Xiao Chen & Wen-zhi Zhang

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  1. Xin-wen Wang
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Correspondence to Wen-zhi Zhang.

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Wang, Xw., Sun, Yj., Chen, X. et al. Interleukin-4-induced FABP4 promotes lipogenesis in human skeletal muscle cells by activating the PPAR γ signaling pathway. Cell Biochem Biophys 80, 355–366 (2022). https://doi.org/10.1007/s12013-022-01063-7

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