Adipogenesis of adipose-derived stem cells may be regulated via the cytoskeleton at physiological oxygen levels in vitro.
Adipogenesis of adipose-derived stem cells may be regulated via the cytoskeleton at physiological oxygen levels in vitro.
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DOI：
10.1186/scrt230
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发表时间：
2013-07-09
影响因子：
7.5
通讯作者：
Kuo CK
中科院分区：
文献类型：
--
作者：
Schiller ZA;Schiele NR;Sims JK;Lee K;Kuo CK
肥胖是白色脂肪组织的过度扩张，是几种严重健康问题的主要风险因素，包括糖尿病、心血管疾病和癌症。对抗肥胖和相关疾病的努力需要了解脂肪形成的基础生物学。然而，体外研究并未产生通常在体内观察到的脂质组成和形态，这可能是因为体外条件并不能真正代表体内脂肪组织形成。在体外，低氧张力和细胞骨架张力已被证明是独立调节脂肪形成，但在体内，这两个因素同时影响分化。本研究的目的是探讨生理氧张力对细胞骨架张力介导的脂肪形成的影响。在环境（20%）和生理（5%）氧条件下分化脂肪来源的干细胞（ASC），并用细胞骨架抑制剂，细胞松弛素D或blebbistatin处理。根据基因表达和脂肪细胞代谢功能评估脂肪生成。脂肪组织代谢标志物（甘油-3-磷酸脱氢酶（GPDH）和甘油三酯）显着下调生理氧水平。通过使用化学抑制剂（细胞松弛素D或blebbistatin）降低细胞骨架张力，导致脂肪形成基因表达（过氧化物酶体增殖物激活受体γ（PPARγ）、脂蛋白脂肪酶（LPL）和脂肪酸结合蛋白4（FABP 4））和代谢标志物上调，与氧水平无关。细胞松弛素D和blebbistatin治疗通过不同的机制改变了细胞骨架组织和相关的张力;然而，这两种情况对脂肪形成有相似的影响，表明ASCs中生理性氧介导的脂肪形成调节部分受细胞骨架张力调节。这些结果表明，细胞骨架和氧张力之间的相互作用影响脂肪细胞的成脂分化。
Obesity, which is excessive expansion of white adipose tissue, is a major risk factor for several serious health issues, including diabetes, cardiovascular disease and cancer. Efforts to combat obesity and related diseases require understanding the basic biology of adipogenesis. However, in vitro studies do not result in lipid composition and morphology that are typically seen in vivo, likely because the in vitro conditions are not truly representative of in vivo adipose tissue formation. In vitro, low oxygen tension and cytoskeletal tension have been shown to independently regulate adipogenesis, but in vivo, these two factors simultaneously influence differentiation. The purpose of our study was to examine the influence of physiological oxygen tension on cytoskeletal tension-mediated adipogenesis. Adipose-derived stem cells (ASCs) were differentiated under both ambient (20%) and physiological (5%) oxygen conditions and treated with cytoskeletal inhibitors, cytochalasin D or blebbistatin. Adipogenesis was assessed on the basis of gene expression and adipocyte metabolic function. Adipose tissue metabolic markers (glycerol-3-phosphate dehydrogenase (GPDH) and triglycerides) were significantly down-regulated by physiological oxygen levels. Reducing cytoskeletal tension through the use of chemical inhibitors, either cytochalasin D or blebbistatin, resulted in an up-regulation of adipogenic gene expression (peroxisome proliferator-activated receptor γ (PPARγ), lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4)) and metabolic markers, regardless of oxygen levels. Cytochalasin D and blebbistatin treatment altered cytoskeletal organization and associated tension via different mechanisms; however, both conditions had similar effects on adipogenesis, suggesting that physiological oxygen-mediated regulation of adipogenesis in ASCs is modulated, in part, by cytoskeletal tension. These results demonstrated that interactions between the cytoskeleton and oxygen tension influence adipogenic differentiation of ASCs.
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