Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF)
Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF)
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DOI：
10.1054/bjoc.2001.1992
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发表时间：
2001-09-01
影响因子：
8.8
通讯作者：
Tisdale, MJ
中科院分区：
文献类型：
--
作者：
Islam-Ali, B;Khan, S;Tisdale, MJ
从携带MAC 16肿瘤的恶病质小鼠中分离的脂肪细胞对低浓度的异丙肾上腺素和肿瘤衍生的脂质动员因子（LMF）的脂解反应增加了3倍以上。这反映了增强的刺激腺苷酸环化酶的脂肪细胞的质膜组分在这两个因素的存在下。有没有上调的腺苷酸环化酶在响应毛喉素，这表明该效应引起的受体数量或G蛋白表达的变化。免疫印迹的脂肪细胞膜从小鼠轴承MAC 16肿瘤表现出增加的气体表达高达10%的重量损失和一个相互减少Ga。与非恶病质癌症患者相比，癌症相关性体重减轻患者脂肪组织中Gas表达增加，Ga减少。在给予纯LMF的正常小鼠的脂肪组织中以及在体外的3T3L1脂肪细胞中也观察到G蛋白表达的变化。由LMF诱导的G蛋白表达的变化被多不饱和脂肪酸二十碳五烯酸（EPA）减弱。这表明这种肿瘤来源的脂解因子起到使脂肪组织对脂解刺激敏感的作用，并且这种作用被EPA减弱，已知EPA在癌症恶病质中保护脂肪组织。(C)2001年癌症研究运动。
Adipocytes isolated from cachectic mice bearing the MAC 16 tumour showed over a 3-fold increase in lipolytic response to both low concentrations of isoprenaline and a tumour-derived lipid mobilizing factor (LMF). This was reflected by an enhanced stimulation of adenylate cyclase in plasma membrane fractions of adipocytes in the presence of both factors. There was no up-regulation of adenylate cyclase in response to forskolin, suggesting that the effect arose from a change in receptor number or G-protein expression. Immunoblotting of adipocyte membranes from mice bearing the MAC16 tumour showed an increased expression of Gas up to 10% weight loss and a reciprocal decrease in Ga. There was also an increased expression of Gas and a decrease in Ga in adipose tissue from a patient with cancer-associated weight loss compared with a non-cachectic cancer patient. The changes in G-protein expression were also seen in adipose tissue of normal mice administered pure LMF as well as in 3T3L1 adipocytes in vitro. The changes in G-protein expression induced by LMF were attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA), This suggests that this tumour-derived lipolytic factor acts to sensitize adipose tissue to lipolytic stimuli, and that this effect is attenuated by EPA, which is known to preserve adipose tissue in cancer cachexia. (C) 2001 Cancer Research Campaign.