Department of General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of General Internal Medicine and Rheumatology, Gifu Municipal Hospital, Gifu, Japan.
J Endocrinol. 2020 Apr;245(1):65-78. doi: 10.1530/JOE-19-0503.
Despite extensive investigation, the mechanisms underlying adipogenesis are not fully understood. We previously identified proliferative cells in adipose tissue expressing adipocyte-specific genes, which were named small proliferative adipocytes (SPA). In this study, we investigated the characteristics and roles of SPA in adipose tissue. Epididymal and inguinal fat was digested by collagenase, and then SPA were separated by centrifugation from stromal vascular cells (SVC) and mature white adipocytes. To clarify the feature of gene expression in SPA, microarray and real-time PCR were performed. The expression of adipocyte-specific genes and several neuronal genes was increased in the order of SVC < SPA < mature white adipocytes. In addition, proliferin was detected only in SPA. SPA differentiated more effectively into lipid-laden cells than SVC. Moreover, differentiated SPA expressed uncoupling protein 1 and mitochondria-related genes more than differentiated SVC. Treatment of SPA with pioglitazone and CL316243, a specific β3-adrenergic receptor agonist, differentiated SPA into beige-like cells. Therefore, SPA are able to differentiate into beige cells. SPA isolated from epididymal fat (epididymal SPA), but not SPA from inguinal fat (inguinal SPA), expressed a marker of visceral adipocyte precursor, WT1. However, no significant differences were detected in the expression levels of adipocyte-specific genes or neuronal genes between epididymal and inguinal SPA. The ability to differentiate into lipid-laden cells in epididymal SPA was a little superior to that in inguinal SPA, whereas the ability to differentiate into beige-like cells was greater in inguinal SPA than epididymal SPA. In conclusion, SPA may be progenitors of beige cells.
尽管进行了广泛的研究，但脂肪生成的机制仍不完全清楚。我们之前发现表达脂肪细胞特异性基因的增殖细胞存在于脂肪组织中，这些细胞被命名为小增殖脂肪细胞（SPA）。在这项研究中，我们研究了 SPA 在脂肪组织中的特征和作用。用胶原酶消化附睾和腹股沟脂肪，然后通过离心将 SPA 从基质血管细胞（SVC）和成熟的白色脂肪细胞中分离出来。为了阐明 SPA 中基因表达的特征，进行了微阵列和实时 PCR 分析。SVC<SPA<成熟白色脂肪细胞中，脂肪细胞特异性基因和几种神经元基因的表达逐渐增加。此外，增殖素仅在 SPA 中检测到。与 SVC 相比，SPA 更有效地分化为富含脂质的细胞。此外，分化后的 SPA 比分化后的 SVC 更有效地表达解偶联蛋白 1 和与线粒体相关的基因。用吡格列酮和 CL316243（一种特定的β3-肾上腺素能受体激动剂）处理 SPA，可将 SPA 分化为米色样细胞。因此，SPA 能够分化为米色细胞。从附睾脂肪中分离的 SPA（附睾 SPA），但不是腹股沟脂肪中的 SPA（腹股沟 SPA），表达内脏脂肪前体细胞标志物 WT1。然而，附睾和腹股沟 SPA 之间在脂肪细胞特异性基因或神经元基因的表达水平上没有明显差异。附睾 SPA 分化为富含脂质的细胞的能力略优于腹股沟 SPA，而腹股沟 SPA 分化为米色样细胞的能力大于附睾 SPA。总之，SPA 可能是米色细胞的前体细胞。
