Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Int J Mol Sci. 2020 Jun 16;21(12):4283. doi: 10.3390/ijms21124283.
The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the differentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. A detailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function.
胚胎发生过程中脂肪细胞的形成在很大程度上尚未得到充分研究。然而，前脂肪细胞似乎起源于多能间充质基质/干细胞，这些细胞从中胚层迁移到它们的解剖定位。大多数关于脂肪细胞形成（脂肪生成）的研究都使用源自成人干细胞/基质细胞的前脂肪细胞。脂肪生成由两个阶段组成，即承诺和终末分化。这篇综述讨论了信号通路、表观遗传修饰物和转录因子在前脂肪细胞承诺和分化为成熟脂肪细胞中的作用，以及我们对这些过程的理解的局限性。迄今为止，已经描述了有限数量的转录因子、基因和信号通路来调节前脂肪细胞的承诺。原因之一可能是大多数关于脂肪生成的研究都使用了已经承诺向脂肪生成谱系的前脂肪细胞，因此不适合研究前脂肪细胞的承诺。相反，已经描述了十多个分子参与者，包括转录因子、基因、信号通路、表观遗传调节剂和 microRNAs，参与前脂肪细胞向脂肪细胞的分化；然而，只有过氧化物酶体增殖物激活受体 γ 已被证明具有临床相关性。详细了解支持脂肪生成的分子参与者与脂肪组织功能的关系，可能为解决肥胖问题提供新的治疗方法，而不会损害脂肪组织功能。
