Kern P A, Saghizadeh M, Ong J M, Bosch R J, Deem R, Simsolo R B
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
J Clin Invest. 1995 May;95(5):2111-9. doi: 10.1172/JCI117899.
A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents. To examine this paradigm in humans, we studied TNF expression in lean, obese, and reduced-obese human subjects. TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR. TNF protein was quantitated by Western blotting and ELISA in both adipose tissue and the medium surrounding adipose tissue. Using quantitative reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI). There was a significant increase in adipose TNF mRNA levels with increasing adiposity. There was a significant correlation between TNF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initial weight), TNF mRNA levels decreased to 58% of initial levels after weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P < 0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity was measured in these subjects, there was a significant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With weight loss, LPL activity increased to 411% of initial levels. However, the magnitude of the increase in LPL did not correlate with the decrease in TNF. Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese subjects and is decreased by weight loss. In addition, there is an inverse relationship between TNF and LPL expression. These data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL.
先前的一项研究报道，在遗传性肥胖啮齿动物的脂肪组织中，细胞因子肿瘤坏死因子（TNF）的表达增加。为了在人类中研究这一模式，我们对体型瘦、肥胖以及体重减轻后的肥胖人类受试者的TNF表达进行了研究。通过Northern印迹法和聚合酶链反应（PCR）在人脂肪细胞和脂肪组织中证实了TNF信使核糖核酸（mRNA）的存在。通过蛋白质免疫印迹法和酶联免疫吸附测定（ELISA）对脂肪组织及其周围培养基中的TNF蛋白进行了定量分析。使用定量逆转录聚合酶链反应（RT-PCR）检测了39名非糖尿病受试者脂肪组织中的TNF mRNA水平，这些受试者的体重指数（BMI）范围很广。随着肥胖程度的增加，脂肪组织中TNF mRNA水平显著升高。TNF mRNA与体脂百分比之间存在显著相关性（r = 0.46，P < 0.05，n = 23）。在极度肥胖的受试者中，TNF mRNA有下降趋势，但排除BMI > 45 kg/m² 的受试者后，TNF mRNA与BMI之间存在显著相关性（r = 0.37，P < 0.05，n = 32）。此外，体重减轻后脂肪组织中的TNF显著下降。在11名体重减轻了14至66千克（平均34.7千克，占初始体重的26.6%）的肥胖受试者中，体重减轻后TNF mRNA水平降至初始水平的58%（P < 0.005），TNF蛋白降至初始水平的46%（P < 0.02）。已知TNF可抑制脂蛋白脂肪酶（LPL）的活性。当对这些受试者的空腹脂肪组织LPL活性进行测量时，TNF表达与LPL活性之间存在显著的负相关关系（r = -0.39，P < 0.02，n = 39）。随着体重减轻，LPL活性增加至初始水平的411%。然而，LPL增加的幅度与TNF的下降并不相关。因此，TNF在人脂肪细胞中表达。在大多数肥胖受试者中TNF升高，体重减轻后则下降。此外，TNF与LPL表达之间存在负相关关系。这些数据表明，脂肪组织中内源性TNF的表达可能通过增加胰岛素抵抗和降低LPL来帮助某些受试者限制肥胖。
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