Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Bunkyo-Ku, Tokyo 113-8655, Japan.
Br J Dermatol. 2009 Oct;161(4):819-25. doi: 10.1111/j.1365-2133.2009.09272.x. Epub 2009 Apr 30.
Involvement of adipose-derived stem/progenitor/stromal cells (ASCs) in the development of lipomas has been suggested, but the pathogenesis and pathophysiology of this tumour remain unclear.
To analyse cellular and transcriptional characteristics of lipoma tissue compared with normal adipose tissue, further to delineate differentiating features.
For lipoma or normal adipose tissues, we used a new whole-mount staining enabling three-dimensional imaging of nonfixed and nonfrozen adipose tissue. Immunohistochemistry and real-time polymerase chain reaction for obesity-related genes were performed as well as comparative assay of the proliferative and adipogenic capacity of ASCs.
A large number of small adipocytes surrounded by CD34+/lectin- ASCs and increased numbers of Ki67+/CD34+ ASCs indicated enhanced adipogenesis in lipoma compared with normal adipose tissue. In contrast, cellular apoptosis was not enhanced in lipoma, suggesting that the enlargement of lipoma tissue may be due to a positive balance of adipocyte turnover (accelerated adipogenesis combined with nonenhanced apoptosis). Leptin mRNA was upregulated in lipoma, while adiponectin, tumour necrosis factor-alpha and glucose transporter 1 mRNA were downregulated and there were no apparent changes in hypoxia-inducible factor 1alpha, peroxisome proliferator-activated receptor-gamma and plasminogen activator inhibitor-1. These results suggested dysfunction of lipoma adipocytes similar to that in obesity, but indicated that lipoma tissue lacked several obesity-related phenomena such as ischaemia (hypoxia), macrophage infiltration, inflammatory reactions and enhanced glycolysis. ASCs from lipoma and normal adipose tissue showed similar proliferative and adipogenic capacity.
Our findings revealed that lipoma tissue shows a positive balance of adipocyte turnover involving proliferating ASCs and several transcriptional differences from adipose tissue enlargement in obesity.
脂肪来源的干细胞/祖细胞/基质细胞（ASCs）参与脂肪瘤的发生已被提出，但这种肿瘤的发病机制和病理生理学仍不清楚。
分析脂肪瘤组织与正常脂肪组织的细胞和转录特征，进一步阐明其分化特征。
对于脂肪瘤或正常脂肪组织，我们使用一种新的整体染色方法，能够对未固定和未冷冻的脂肪组织进行三维成像。进行了与肥胖相关基因的免疫组织化学和实时聚合酶链反应，以及 ASC 的增殖和成脂能力的比较检测。
大量被 CD34+/凝集素-ASC 包围的小脂肪细胞和增加的 Ki67+/CD34+ASC 表明与正常脂肪组织相比，脂肪瘤中的脂肪生成增强。相比之下，脂肪瘤中细胞凋亡并未增强，这表明脂肪瘤组织的增大可能是由于脂肪细胞更替的正平衡（加速脂肪生成与非增强的凋亡相结合）。脂肪素 mRNA 在脂肪瘤中上调，而脂联素、肿瘤坏死因子-α和葡萄糖转运蛋白 1 mRNA 下调，缺氧诱导因子 1α、过氧化物酶体增殖物激活受体-γ和纤溶酶原激活物抑制剂-1 无明显变化。这些结果表明脂肪瘤脂肪细胞的功能障碍类似于肥胖症中的脂肪细胞，但表明脂肪瘤组织缺乏一些与肥胖相关的现象，如缺血（缺氧）、巨噬细胞浸润、炎症反应和增强的糖酵解。脂肪瘤和正常脂肪组织的 ASC 表现出相似的增殖和成脂能力。
我们的研究结果表明，脂肪瘤组织表现出脂肪细胞更替的正平衡，涉及增殖的 ASC，以及与肥胖症脂肪组织增大相关的几个转录差异。
