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. 2020 Oct 6;30(12):5086–5100. doi: 10.1007/s11695-020-04983-6

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Molecular mechanism of adipogenesis. During the process of mesenchymal stem cells (MSCs) commitment to adipose lineage, WNT1 inducible signaling pathway protein 2(WISP2) presented in the cytosol repressed transcriptional activator zinc finger protein-423 (ZFP423) through formation of a WISP2/ZFP423 complex in cytosol. Bone morphogenetic protein 4 (BMP4) phosphorylates SMAD1/5/8 to dissociate WISP2/ZFP423 complex, making ZFP423 enter into the nucleus and further activates peroxisome proliferator-activated receptor γ (PPARγ). BMP4 inhibitor Gremlin-1 suppresses MSCs by inhibiting BMP4. Likewise, extracellular WISP2 inhibits PPARγ by activating β-catenin. After committed differentiation to adipogenic lineage, EBF transcription factor 1(EBF1), a transcription factor activated by CCAAT-enhancer-binding proteins (C/EBPβ) and C/EBPδ, induces the activation of PPARγ. C/EBPα binds on the promoter region of PPARγ and forms the self-reinforcing regulatory loop to further stimulate adipogenesis. Activated PPARγ heterodimerizes with retinoid X receptor α (RXRα) and promotes transcription of genes involved in adipocyte differentiation and lipid transport