Tissue-Specific Progenitor and Stem Cells Functional Plasticity of Adipose-Derived Stromal Cells During Development of Obesity
Tissue-Specific Progenitor and Stem Cells Functional Plasticity of Adipose-Derived Stromal Cells During Development of Obesity
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2016
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通讯作者：
Xiang-yang Zhu;A. Eirin;J. Woollard;L. Hickson;Dong Sun;A. Lerman;Lilach O. LERMANa
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作者：
Xiang-yang Zhu;A. Eirin;J. Woollard;L. Hickson;Dong Sun;A. Lerman;Lilach O. LERMANa
肥胖是许多慢性疾病的主要危险因素，包括糖尿病、心血管疾病和癌症。脂肪块的扩张需要源自多能脂肪源性基质细胞（ASC）的脂肪细胞前体细胞，而这些细胞反过来也参与修复活动。 ASC 功能可能在疾病环境中下降，但尚不清楚 ASC 功能在肥胖发展过程中是否发生变化。我们测试了肥胖代谢紊乱发展过程中微环境炎症变化影响 ASC 功能的假设。家猪饲喂致动脉粥样硬化 (n = 7) 或正常 (n = 7) 饮食 16 周。饮食8、12和16周后收集腹部脂肪组织活检用于ASC分离和原位ASC和肿瘤坏死因子-a（TNF-a）的免疫组织化学分析。评估了 ASC 的增殖、分化和抗炎功能的纵向变化。第 16 周时，肥胖猪脂肪组织中 TNF-a 表达上调，伴随着脂肪组织中脂肪细胞祖细胞 (CD24/CD34) 数量的增加和脂肪细胞尺寸的增大。在体外，肥胖猪的ASC表现出增强的成脂和成骨倾向，抗TNF-a处理可消除这种倾向，而用TNF-a处理的瘦ASC则显示出增强的脂肪生成。此外，与瘦猪ASC相比，肥胖ASC表现出衰老增加，而其免疫调节能力得以保留。脂肪组织炎症促进驻留脂肪细胞祖细胞的增加，上调 TNF-a 增强 ASC 脂肪生成。因此，脂肪组织抗炎策略可能是减轻肥胖及其并发症的新目标。干细胞转化医学 2016 年；5:893–900
Obesity isamajor risk factor foranumberofchronicdiseases, includingdiabetes, cardiovasculardiseases, and cancer. Expansion of the adiposemass requires adipocyte precursor cells that originate frommultipotent adipose-derived stromal cells (ASCs), which in turn also participate in repair activities. ASC function might decline in a disease milieu, but it remains unclear whether ASC function varies during the development of obesity.We tested the hypothesis thatmicroenvironmental inflammatory changes during development of metabolic disorders in obesity affect ASC function. Domestic pigs were fed with an atherogenic (n = 7) or normal (n = 7) diet for 16weeks. Abdominal adipose tissue biopsieswere collected after 8, 12, and 16 weeks of diet for ASC isolation and immunohistochemistry of in situ ASCs and tumor necrosis factor-a (TNF-a). Longitudinal changes in proliferation, differentiation, and anti-inflammatory functions of ASCs were assessed. At 16 weeks, upregulated TNF-a expression in adipose tissue from obese pigs was accompanied by increased numbers of adipocyte progenitors (CD24/CD34) in adipose tissue and enlarged adipocyte size. In vitro, ASCs from obese pigs showed enhanced adipogenic and osteogenic propensity,whichwas abolishedbyanti-TNF-a treatment,whereas leanASCs treatedwith TNF-a showedenhancedadipogenesis.Furthermore,obeseASCsshowedincreasedsenescencecompared with lean ASCs, whereas their immunomodulatory capacity was preserved. Adipose tissue inflammation promotes an increase in resident adipocyte progenitors and upregulated TNF-a enhances ASC adipogenesis. Thus, adipose tissue anti-inflammatory strategiesmight be anovel target to attenuate obesity and its complications. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:893–900