Cellular and molecular features of lipoma tissue: comparison with normal adipose tissue

BACKGROUND: 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. OBJECTIVES: To analyse cellular and transcriptional characteristics of lipoma tissue compared with normal adipose tissue, further to delineate differentiating features. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.