Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell.

Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell.
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DOI:
10.1371/journal.pone.0036569
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Luconi M
Luconi M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Baglioni S;Cantini G;Poli G;Francalanci M;Squecco R;Di Franco A;Borgogni E;Frontera S;Nesi G;Liotta F;Lucchese M;Perigli G;Francini F;Forti G;Serio M;Luconi M

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代谢病理主要源于脂肪组织(AT)功能障碍。AT差异与皮下(SAT)和内脏网膜(VAT)垫中的脂肪储存解剖分布相关。我们解决的问题,这两个隔室之间的功能差异是否可能存在于早期的脂肪干细胞(ASC),而不是局限于成熟的脂肪细胞。使用特定的人ASC模型,我们评估了平行的腹部SAT-(S-ASC)和VAT-(V-ASC)配对活检组织中ASC的增殖/分化,以及ASC及其体外衍生脂肪细胞的电生理特性和功能活性。在两个ASC群体之间观察到增殖和成脂潜力的显著差异,S-ASC具有显著高于V-ASC的生长速率和成脂潜力,并且产生更多功能和更好组织的脂肪细胞。据我们所知,这是第一次对ASC和衍生脂肪细胞进行全面的电生理学分析,显示了电生理学特性,如膜电位、电容和K+电流参数,这些参数证实了S-ASC及其衍生脂肪细胞具有更好的功能。我们证明了S-ASC衍生的脂肪细胞分泌脂联素的能力更强,对脂解的敏感性降低。这些特征可以解释SAT和VAT之间观察到的代谢差异。我们的研究结果表明,增值税和SAT功能的差异起源于成人ASC的水平,保持其脂肪垫的起源的记忆。这种干细胞的差异可以解释不同的脂肪储存对代谢功能障碍的发展的敏感性,并可能代表特定治疗方法的合适靶点。
Metabolic pathologies mainly originate from adipose tissue (AT) dysfunctions. AT differences are associated with fat-depot anatomic distribution in subcutaneous (SAT) and visceral omental (VAT) pads. We address the question whether the functional differences between the two compartments may be present early in the adipose stem cell (ASC) instead of being restricted to the mature adipocytes. Using a specific human ASC model, we evaluated proliferation/differentiation of ASC from abdominal SAT-(S-ASC) and VAT-(V-ASC) paired biopsies in parallel as well as the electrophysiological properties and functional activity of ASC and their in vitro-derived adipocytes. A dramatic difference in proliferation and adipogenic potential was observed between the two ASC populations, S-ASC having a growth rate and adipogenic potential significantly higher than V-ASC and giving rise to more functional and better organized adipocytes. To our knowledge, this is the first comprehensive electrophysiological analysis of ASC and derived-adipocytes, showing electrophysiological properties, such as membrane potential, capacitance and K+-current parameters which confirm the better functionality of S-ASC and their derived adipocytes. We document the greater ability of S-ASC-derived adipocytes to secrete adiponectin and their reduced susceptibility to lipolysis. These features may account for the metabolic differences observed between the SAT and VAT. Our findings suggest that VAT and SAT functional differences originate at the level of the adult ASC which maintains a memory of its fat pad of origin. Such stem cell differences may account for differential adipose depot susceptibility to the development of metabolic dysfunction and may represent a suitable target for specific therapeutic approaches.
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