Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia
Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia
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DOI：
10.1126/science.1198973
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发表时间：
2011-07-08
期刊：
影响因子：
56.9
通讯作者：
Hoefler, Gerald
中科院分区：
文献类型：
--
作者：
Das, Suman K.;Eder, Sandra;Hoefler, Gerald
恶病质是一种多因素消耗综合征，最常见于癌症患者，其特征是脂肪和肌肉质量的不受控制的损失。我们发现，通过基因消除脂肪甘油三酯脂肪酶（Atgl）或脂肪敏感性脂肪酶（Hsl）来抑制脂解可改善癌症相关恶病质（CAC）的某些特征。在野生型C57 BL/6小鼠中，注射刘易斯肺癌或B16黑色素瘤细胞导致肿瘤生长、白色脂肪组织（WAT）损失和腓肠肌显著减少。与此相反，Atgl缺陷的小鼠肿瘤抵抗增加WAT脂解，肌细胞凋亡和蛋白酶体肌肉降解，并保持正常的脂肪和腓肠肌质量。具有肿瘤的hsl缺陷小鼠也受到保护，尽管程度较低。因此，功能性脂解在CAC的发病机制中是必不可少的。代谢脂肪酶的药理学抑制可能有助于预防恶病质。
Cachexia is a multifactorial wasting syndrome most common in patients with cancer that is characterized by the uncontrolled loss of adipose and muscle mass. We show that the inhibition of lipolysis through genetic ablation of adipose triglyceride lipase (Atgl) or hormone-sensitive lipase (Hsl) ameliorates certain features of cancer-associated cachexia (CAC). In wild-type C57BL/6 mice, the injection of Lewis lung carcinoma or B16 melanoma cells causes tumor growth, loss of white adipose tissue (WAT), and a marked reduction of gastrocnemius muscle. In contrast, Atgl-deficient mice with tumors resisted increased WAT lipolysis, myocyte apoptosis, and proteasomal muscle degradation and maintained normal adipose and gastrocnemius muscle mass. Hsl-deficient mice with tumors were also protected although to a lesser degree. Thus, functional lipolysis is essential in the pathogenesis of CAC. Pharmacological inhibition of metabolic lipases may help prevent cachexia.