[肿瘤坏死因子-α诱导的胰岛素抵抗对小鼠脂肪甘油三酯脂肪酶的影响]
[Effects of tumor necrosis factor-alpha induced insulin resistance on adipose triglyceride lipase in mice].
作者信息
Cheng Yu-Lan, Li Ling, Yang Gang-Yi, Shi Shao-Chuan, Chen Yu, Zhu Wei, Sun Xun
机构信息
Key Laboratory of Laboratory Medical Diagnostics in Ministry of Education, Department of Clinical Biochemistry, Chongqing Medical University, Chongqing 400016, China.
出版信息
Zhonghua Yi Xue Za Zhi. 2008 Sep 9;88(34):2417-21.
OBJECTIVE
To investigate the effects of tumor necrosis factor (TNF)-alpha induced insulin resistance (IR) on glucose and lipid metabolism and adipose triglyceride lipase (ATGL).
METHODS
Forty male C57BL/6J mice were randomly divided into 2 equal groups: TNF-alpha group with undergoing intraperitoneal injection of TNF-alpha 6 microg x kg(-1) x d(-1) for 7 days and normal control (NC) group with saline injection. Hyperinsulinemic-euglycemic clamp technique combined with 2-deoxy-[(3)H] glucose as a tracer was used on 20 mice, 10 from each group, to examine the fasting blood glucose (FBG), plasma insulin (INS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA). The glucose infusion rate (GIR) was recorded. Other 20 mice, 10 in each group, were killed with their adipose and/or muscle tissues taken out. RT-PCR was used to detect the mRNA expression of ATGL, hormone-sensitive lipase (HSL), carnitine palmitoyl transferase-1 (CPT-1), and peroxisome proliferator activated receptor-gamma (PPARgamma). Western blotting was used to measure the protein expression of ATGL. Muscle glucose uptake (MGU) was measured.
RESULTS
After TNF-alpha treatment, the FBG, plasma INS, and FFA were significantly elevated in the TNF group compared with the NC group (all P < 0.05). During the steady-state of clamp test, the plasma INS level of the TNF group was (341.7 +/- 17.7) mU/L, significantly higher than that of the NC group [(84.7 +/- 5.5) mU/L, P < 0.01]. The FFA level of the TNF group was (0.82 +/- 0.03) mmol/L, significantly higher than that of the NC group [(0.43 +/- 0.07) mmol/L, P < 0.01]. The GIR of the TNF group was (39.1 +/- 2.3) mg x kg(-1)x min(-1), significantly lower than that of the NC group [(54.2 +/- 2.2) mg x kg(-1) x min(-1), P < 0.01]. The MGU level of the TNF group was (15.8 +/- 1.7) micromol.100 g(-1) x min(-1), significantly lower than that of the NC group [(20.9 +/- 2.5) micromol.100 g(-1) x min(-1), P < 0.01]. The ATGL mRNA expression level in adipose tissues of the TNF group was (0.85 +/- 0.09), significantly lower than that of the NC group (1.37 +/- 0.12, P < 0.01). The ATGL protein expression level of the TNF group was 0.53 +/- 0.03, significantly lower than that of the NC group (0.65 +/- 0.05, P < 0.05). The PPARgamma mRNA expression level in adipose tissues of the TNF group was 0.83 +/- 0.07, significantly lower than that of the NC group (1.07 +/- 0.07, P < 0.05).
CONCLUSION
In TNF-alpha induced insulin resistance, AGTL may be involved in the pathways of lipid metabolism.
目的
探讨肿瘤坏死因子（TNF）-α诱导的胰岛素抵抗（IR）对糖脂代谢及脂肪甘油三酯脂肪酶（ATGL）的影响。
方法
将40只雄性C57BL/6J小鼠随机分为2组，每组20只：TNF-α组腹腔注射TNF-α 6 μg·kg⁻¹·d⁻¹，连续7天；正常对照组注射生理盐水。对每组10只小鼠采用高胰岛素-正糖钳夹技术结合2-脱氧-[(³)H]葡萄糖作为示踪剂，检测空腹血糖（FBG）、血浆胰岛素（INS）、总胆固醇（TC）、甘油三酯（TG）和游离脂肪酸（FFA），记录葡萄糖输注速率（GIR）。另取每组10只小鼠处死，取出脂肪和/或肌肉组织，采用RT-PCR检测ATGL、激素敏感性脂肪酶（HSL）、肉碱棕榈酰转移酶-1（CPT-1）和过氧化物酶体增殖物激活受体-γ（PPARγ）的mRNA表达，采用蛋白质印迹法检测ATGL的蛋白表达，检测肌肉葡萄糖摄取（MGU）。
结果
与正常对照组相比，TNF-α处理后TNF组的FBG、血浆INS和FFA显著升高（均P < 0.05）。在钳夹试验稳态期，TNF组血浆INS水平为（341.7 ± 17.7）mU/L，显著高于正常对照组[（84.7 ± 5.5）mU/L，P < 0.01]。TNF组FFA水平为（0.82 ± 0.03）mmol/L，显著高于正常对照组[（0.43 ± 0.07）mmol/L，P < 0.01]。TNF组GIR为（39.1 ± 2.3）mg·kg⁻¹·min⁻¹，显著低于正常对照组[（54.2 ± 2.2）mg·kg⁻¹·min⁻¹，P < 0.01]。TNF组MGU水平为（15.8 ± 1.7）μmol·100 g⁻¹·min⁻¹，显著低于正常对照组[（20.9 ± 2.5）μmol·100 g⁻¹·min⁻¹，P < 0.01]。TNF组脂肪组织中ATGL mRNA表达水平为（0.85 ± 0.09），显著低于正常对照组（1.37 ± 0.12，P < 0.01）。TNF组ATGL蛋白表达水平为0.53 ± 0.03，显著低于正常对照组（0.65 ± 0.05，P < 0.05）。TNF组脂肪组织中PPARγ mRNA表达水平为0.83 ± 0.07，显著低于正常对照组（1.07 ± 0.07，P < 0.05）。
结论
在TNF-α诱导的胰岛素抵抗中，AGTL可能参与脂质代谢途径。
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