THE EXPRESSION OF TUMOR-NECROSIS-FACTOR IN HUMAN ADIPOSE-TISSUE - REGULATION BY OBESITY, WEIGHT-LOSS, AND RELATIONSHIP TO LIPOPROTEIN-LIPASE
THE EXPRESSION OF TUMOR-NECROSIS-FACTOR IN HUMAN ADIPOSE-TISSUE - REGULATION BY OBESITY, WEIGHT-LOSS, AND RELATIONSHIP TO LIPOPROTEIN-LIPASE
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DOI：
10.1172/jci117899
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发表时间：
1995-05-01
影响因子：
15.9
通讯作者：
SIMSOLO, RB
中科院分区：
文献类型：
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作者：
KERN, PA;SAGHIZADEH, M;SIMSOLO, RB
先前的一项研究报道了遗传性肥胖啮齿动物脂肪组织中细胞因子TNF的表达增加，为了在人类中检验这一范式，我们研究了瘦弱，肥胖和减轻肥胖的人类受试者中TNF的表达，通过Northern blotting和PCR证实了TNF mRNA在人类脂肪细胞和脂肪组织中，通过Western blotting和ELISA在脂肪组织和脂肪组织周围的培养基中定量检测TNF蛋白。使用定量逆转录酶聚合酶链反应(rt - PCR)、肿瘤坏死因子mRNA水平检查39非糖尿病患者脂肪组织的主题,涵盖范围广泛的身体质量指数(BMI),有一个显著增加与增加肥胖,脂肪肿瘤坏死因子mRNA水平之间存在着显著相关肿瘤坏死因子mRNA和身体脂肪百分比(r = 0.46, P < 0.05, n = 23),肿瘤坏死因子mRNA倾向于减少非常肥胖的研究对象,但当受试者体重指数> 45公斤/米(2)被排除在外,TNF mRNA与BMI有显著相关性（r = 0.37, P < 0.05, n = 32）。此外，脂肪TNF随体重减轻而显著下降，在11名体重减轻14至66公斤（平均34.7公斤，或初始体重的26.6%）的肥胖受试者中，体重减轻后TNF mRNA水平下降到初始水平的58% (P < 0.005)， TNF蛋白下降到初始水平的46% (P < 0.02)， TNF已知抑制LPL活性。当在这些受试者中测量空腹脂肪LPL活性时，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活性增加到初始水平的411%，然而，LPL增加的幅度与TNF的降低无关，因此，TNF在人类脂肪细胞中表达，TNF在大多数肥胖受试者中升高，并随着体重减轻而降低。这些数据表明，脂肪组织中内源性TNF表达可能有助于限制某些受试者的肥胖，可能是通过增加胰岛素抵抗和降低LPL。
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/m(2) 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.