Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots
Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots
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DOI：
10.1152/ajpendo.00265.2004
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发表时间：
2005-01-01
影响因子：
5.1
通讯作者：
Kirkland, JL
中科院分区：
文献类型：
--
作者：
Tchkonia, T;Tchoukalova, YD;Kirkland, JL
脂肪库的功能和大小各不相同。脂肪细胞发育的前脂肪细胞表现出明显的区域性特征，并在培养中持续存在。人腹部皮下培养的前脂肪细胞比网膜前脂肪细胞经历更广泛的脂质积聚、更高的成脂转录因子表达和更少的TNF-α诱导的凋亡。我们发现皮下和肠系膜的前脂肪细胞比大网膜的前脂肪细胞具有更高的复制潜能。在对来自单个前脂肪细胞的集落的研究中，发现了两种前脂肪细胞亚型，一种能够更广泛地复制、分化和脂肪形成转录因子表达，并且比另一种响应于TNF-α的凋亡更少。前者在皮下和肠系膜比网膜前脂肪细胞群中更丰富，可能有助于复制，分化和凋亡的区域变化。这两种亚型都存在于来源于稳定表达端粒酶的单个人前脂肪细胞的菌株中，证实这两种亚型都是前脂肪细胞谱系。在亚克隆任一亚型的细胞后，发现两种亚型，表明亚型之间可以发生转换。因此，具有不同细胞动力学特性的前脂肪细胞亚型的比例在不同的库中变化，可能允许在发育过程中通过亚型选择的组织可塑性。此外，肠系膜前脂肪细胞的细胞动力学特征与网膜细胞不同，表明内脏脂肪库在功能上并不均匀。
Fat depots vary in function and size. The preadipocytes that fat cells develop from exhibit distinct regional characteristics that persist in culture. Human abdominal subcutaneous cultured preadipocytes undergo more extensive lipid accumulation, higher adipogenic transcription factor expression, and less TNF-alpha-induced apoptosis than omental preadipocytes. We found higher replicative potential in subcutaneous and mesenteric than in omental preadipocytes. In studies of colonies arising from single preadipocytes, two preadipocyte subtypes were found, one capable of more extensive replication, differentiation, and adipogenic transcription factor expression and less apoptosis in response to TNF-alpha than the other. The former was more abundant in subcutaneous and mesenteric than in omental preadipocyte populations, potentially contributing to regional variation in replication, differentiation, and apoptosis. Both subtypes were found in strains derived from single human preadipocytes stably expressing telomerase, confirming that both subtypes are of preadipocyte lineage. After subcloning of cells of either subtype, both subtypes were found, indicating that switching can occur between subtypes. Thus proportions of preadipocyte subtypes with distinct cell-dynamic properties vary among depots, potentially permitting tissue plasticity through subtype selection during development. Furthermore, mesenteric preadipocyte cell-dynamic characteristics are distinct from omental cells, indicating that visceral fat depots are not functionally uniform.