生物谷援引新华网：瑞典卡罗林斯卡医学院的专家最近发现了导致部分癌症患者日渐消瘦的机理，并找到了可抑制癌症患者消瘦的物质。
研究人员在临床中发现，一些癌症患者会出现不明原因的消瘦。之后，对这类患者的脂肪组织进行分析研究，结果发现脂肪细胞中一种名为脂肪酶的蛋白质代谢失调，从而导致脂肪消耗过快。
研究人员已经从一种治疗血脂失调和糖尿病的药物中发现了可以抑制消瘦的物质。该研究项目负责人彼得·阿纳表示，大多数癌症的发生都会伴有不同程度的消瘦症状，而且消瘦也会使得癌症的治疗效果下降。如果能研制出抑制消瘦的药物，将对癌症患者战胜病魔大有帮助。
这项研究成果刊登在最新一期美国《癌症研究》（Cancer Research）杂志上。
原始出处:
Cancer Research 67, 5531-5537, June 1, 2007. doi: 10.1158/0008-5472.CAN-06-4585
Clinical Research
Mechanism of Increased Lipolysis in Cancer Cachexia
Thorhallur Agustsson1, Mikael Rydén2, Johan Hoffstedt2, Vanessa van Harmelen2, Andrea Dicker2, Jurga Laurencikiene2, Bengt Isaksson1, Johan Permert1 and Peter Arner2
Departments of 1 Surgery and 2 Medicine, Karolinska Institutet at Karolinska University Hospital, Stockhom, Sweden
Requests for reprints: Peter Arner, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. Phone: 46-8-585-82342; Fax: 46-8-585-82407; E-mail: peter.arner@ki.se .
Loss of fat mass is a key feature of cancer cachexia and has been attributed to increased adipocyte lipolysis. The mechanism behind this alteration is unknown and was presently investigated. We studied mature s.c. fat cells and differentiated preadipocytes from 26 cancer patients with and without cachexia. Hormone-induced lipolysis and expression of lipolysis-regulating genes were determined together with body composition and in vivo lipolytic activity (fasting plasma glycerol or fatty acids related to body fat). Body fat was reduced by 40% and in vivo lipolytic activity was 2-fold increased in cachexia (P = 0.001). In mature adipocytes, the lipolytic effects of catecholamines and natriuretic peptide were 2- to 3-fold increased in cachexia (P < 0.001). This was completely counteracted by inhibiting the rate-limiting lipolysis enzyme hormone-sensitive lipase (HSL). In cachexia, the expression levels of HSL mRNA and protein were increased by 50% and 100%, respectively (P = 0.005–0.03), which strongly correlated with in vitro lipolytic stimulation (r = 0.7–0.9). The antilipolytic effect of insulin in mature fat cells and the stimulated lipolytic effect in differentiated preadipocytes were unaltered in cachexia. Patients who lost weight due to other factors than cancer cachexia had no change in adipocyte lipolysis. In conclusion, adipocyte lipolysis is increased in cancer cachexia not due to nonepigenic factors or to weight loss per se, but most probably because of enhanced expression and function of adipocyte HSL. The selective inhibition of this enzyme may prevent fat loss in cancer patients. [Cancer Res 2007;67(11):5531–7]
