Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans

Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans
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DOI:
10.1152/ajpendo.00110.2003
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发表时间:
2003-09-01
影响因子:
5.1
通讯作者:
Richelsen, B
Richelsen, B
中科院分区:
医学2区
文献类型:
--
作者:
Bruun, JM;Lihn, AS;Richelsen, B

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脂联素是一种脂肪组织特异性蛋白,在循环中大量存在,并被认为与胰岛素敏感性和动脉粥样硬化的发展有关。由于细胞因子被认为是调节脂联素,本研究的目的是研究脂联素和三种脂肪组织来源的细胞因子(IL-6,IL-8和TNF-α)之间的相互作用。该研究分为以下三个子研究:1)肥胖受试者[平均体重指数(BMI):39.7 kg/m(2),n = 6]减肥前后脂肪组织活检中的血浆脂联素和mRNA水平; 2)肥胖男性的血浆脂联素水平。(平均BMI:38.7 kg/m2,n = 19)与消瘦男性(平均BMI:23.4 kg/m2,n = 10)相比,在减肥前后;和3)在体外直接影响IL-6,IL- 8,和TNF-α对脂肪组织培养的脂联素mRNA水平。结果是:1)体重减轻导致51%的血浆脂联素水平升高(P < 0.05),(P < 0.05)脂肪组织mRNA水平升高; 2)血浆脂联素水平升高53%,血浆脂联素水平与肥胖、胰岛素敏感性、IL-6呈负相关(P < 0.01); TNF-α(P < 0.01)和IL- 6及其可溶性受体(P < 0.05)可降低脂联素mRNA的表达。体内血浆脂联素和细胞因子之间的负相关关系以及体外马槟榔诱导的脂联素mRNA的减少表明内源性细胞因子可能抑制脂联素。这对于细胞因子(例如,IL- 6)与胰岛素抵抗和动脉粥样硬化。
Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-alpha). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [ mean body mass index (BMI): 39.7 kg/m(2), n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m(2), n = 19) compared with lean men (mean BMI: 23.4 kg/m(2), n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL- 8, and TNF-alpha on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% (P < 0.05) increase in plasma adiponectin and a 45% (P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% (P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-alpha (P < 0.01) and IL- 6 plus its soluble receptor (P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL- 6) and insulin resistance and atherosclerosis.