Hirai K, Hussey H J, Barber M D, Price S A, Tisdale M J
Department of Obstetrics and Gynecology, Osaka City University Medical School, Japan.
Cancer Res. 1998 Jun 1;58(11):2359-65.
We have previously shown human lipid-mobilizing factor (LMF) to be homologous with the plasma protein Zn-alpha2-glycoprotein in amino acid sequence, electrophoretic mobility, and immunoreactivity. In this study, both LMF and Zn-alpha2-glycoprotein have been shown to stimulate glycerol release from isolated murine epididymal adipocytes with a comparable dose-response profile. Both LMF and Zn-alpha2-glycoprotein caused a stimulation of adenylate cyclase in murine adipocyte plasma membranes in a GTP-dependent process, with maximum stimulation at 0.1 microM GTP and with saturation at protein concentrations of >5 microg/assay. Administration of LMF to exbreeder male mice over a 89-h period produced a decrease in body weight without a change in food and water intake. Body composition analysis showed a 42% reduction in carcass lipid when compared with controls. Treatment of ob/ob mice with human LMF over a 160-h period also produced a decrease in body weight, with a 19% reduction in carcass fat, without a change in body water or nonfat mass. Serum levels of glycerol and 3-hydroxybutyrate were significantly increased, as was oxygen uptake by interscapular brown adipose tissue, providing evidence of increased lipid mobilization and utilization. Human white adipocytes responded to both LMF and isoprenaline to the same extent, although the maximal response was lower than that for murine white adipocytes. These results suggest that LMF not only has the capacity to induce lipid mobilization and catabolism in mice, but it also has the potential to exert similar effects in cachectic cancer patients.
我们之前已表明，人脂质动员因子（LMF）在氨基酸序列、电泳迁移率和免疫反应性方面与血浆蛋白锌-α2-糖蛋白同源。在本研究中，已证明LMF和锌-α2-糖蛋白均可刺激分离的小鼠附睾脂肪细胞释放甘油，且剂量反应曲线相似。LMF和锌-α2-糖蛋白均在GTP依赖性过程中刺激小鼠脂肪细胞质膜中的腺苷酸环化酶，在0.1 microM GTP时刺激最大，在蛋白浓度>5微克/测定时达到饱和。对繁殖期过后的雄性小鼠连续89小时给予LMF，体重下降，而食物和水摄入量无变化。身体成分分析显示，与对照组相比，胴体脂质减少了42%。对ob/ob小鼠连续160小时给予人LMF也导致体重下降，胴体脂肪减少19%，而身体水分或无脂体重无变化。血清甘油和3-羟基丁酸水平显著升高，肩胛间棕色脂肪组织的氧摄取也增加，这证明脂质动员和利用增加。人白色脂肪细胞对LMF和异丙肾上腺素的反应程度相同，尽管最大反应低于小鼠白色脂肪细胞。这些结果表明，LMF不仅有能力在小鼠中诱导脂质动员和分解代谢，而且有可能在恶病质癌症患者中发挥类似作用。
