TNFa release by the nonfat cells of human adipose tissue

TNFa release by the nonfat cells of human adipose tissue
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DOI:
10.1038/sj.ijo.0802594
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发表时间:
2004-04-01
影响因子:
4.9
通讯作者:
Madan, AK
Madan, AK
中科院分区:
医学2区
文献类型:
--
作者:
Fain, JN;Bahouth, SW;Madan, AK

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目的:主要目的是研究人类脂肪组织中脂肪细胞与非脂肪细胞在释放免疫反应性肿瘤坏死因子-α(TNFα)方面的相对重要性。第二个目的是检查体重指数 (BMI) 与原代培养中孵育 48 小时的人皮下和内脏脂肪组织外植体随后释放的脂联素和 TNFα 之间的相关性。 结果:我们发现原代培养中的人脂肪组织外植体在 48 小时孵育的前 4 小时内观察到 TNFα 的最大释放。人类脂肪组织外植体在 4 小时孵育后释放到培养基中的 TNFα 超过 95% 来自脂肪组织中存在的非脂肪细胞。胶原酶消化期间释放的非脂肪细胞释放的 TNFα 略高于胶原酶消化后存在于脂肪组织基质中的细胞。组合基质和分离的非脂肪细胞释放的 TNFα 大于组织外植体释放的 TNFα,表明胶原酶消化诱导了一些上调。免疫反应性 TNFα 从培养基中消失,半衰期约为 10 小时。组织外植体释放的 TNFα 与脂肪供体的 BMI 之间存在 0.79 的正相关系数,BMI 与脂肪细胞释放之间的相关系数为 0.52。 TNFα 释放与脂肪组织的脂联素释放呈负相关 [-0.60]。在人脂肪组织外植体培养4小时后,TNFα的释放远低于脂联素或IL-6的释放,并且低于纤溶酶原激活剂抑制剂-1、肝细胞生长因子或瘦素的释放。脂多糖可增强 4 小时内的 TNFα 释放,而环加氧酶 2 抑制剂则可抑制 TNFα 的释放。结论:肥胖人体脂肪组织释放的 TNFα 主要是由于脂肪组织中存在非脂肪细胞。 TNFα 是一种短暂的脂肪因子,其在原代培养物中由人体脂肪组织释放,与脂肪供体的 BMI 相关。
OBJECTIVE: The primary aim was to investigate the relative importance of the adipocytes vs the nonfat cells present in human adipose tissue with respect to release of immunoreactive tumor necrosis factor-alpha (TNFalpha). The second aim was to examine the correlation between body mass index ( BMI) and the subsequent release of adiponectin and TNFalpha by explants of human subcutaneous and visceral adipose tissue incubated in primary culture for 48 h.RESULTS: We found that the maximal release of TNFalpha was seen during the first 4 h of a 48- h incubation by explants of human adipose tissue in primary culture. Over 95% of the TNFalpha released to the medium by human adipose tissue explants over a 4- h incubation came from the nonfat cells present in the adipose tissue. The release of TNFalpha by the nonfat cells released during collagenase digestion was slightly higher than that by the cells present in the adipose tissue matrix after collagenase digestion. TNFalpha release by the combined matrix and isolated nonfat cells was greater than that by explants of tissue indicating some upregulation induced by collagenase digestion. Immunoreactive TNFalpha disappeared from the medium with a half- time of approximately 10 h. There was a positive correlation coefficient of 0.79 between TNFalpha release by tissue explants and the BMI of the fat donors as well as a correlation of 0.52 between BMI and release by adipocytes. TNFalpha release negatively correlated [ - 0.60] with adiponectin release by adipose tissue. The release of TNFalpha was far less than that of adiponectin or IL- 6, and less than that of plasminogen activator inhibitor- 1, hepatocyte growth factor, or leptin over a 4- h incubation of human adipose tissue explants. TNFalpha release over 4 h was enhanced by lipopolysaccharide and inhibited by a cyclooxygenase- 2 inhibitor.CONCLUSION: The release of TNFalpha by adipose tissue of obese humans is primarily due to the nonfat cells present in adipose tissue. TNFalpha is a short- lived adipokine whose release by human adipose tissue in primary culture correlates with the BMI of the fat donors.