生物谷援引新華網(wǎng)：瑞典卡羅林斯卡醫(yī)學(xué)院的專家最近發(fā)現(xiàn)了導(dǎo)致部分癌癥患者日漸消瘦的機(jī)理,，并找到了可抑制癌癥患者消瘦的物質(zhì),。
研究人員在臨床中發(fā)現(xiàn)，一些癌癥患者會(huì)出現(xiàn)不明原因的消瘦,。之后,，對(duì)這類患者的脂肪組織進(jìn)行分析研究，結(jié)果發(fā)現(xiàn)脂肪細(xì)胞中一種名為脂肪酶的蛋白質(zhì)代謝失調(diào),，從而導(dǎo)致脂肪消耗過快,。
研究人員已經(jīng)從一種治療血脂失調(diào)和糖尿病的藥物中發(fā)現(xiàn)了可以抑制消瘦的物質(zhì)。該研究項(xiàng)目負(fù)責(zé)人彼得·阿納表示,，大多數(shù)癌癥的發(fā)生都會(huì)伴有不同程度的消瘦癥狀,，而且消瘦也會(huì)使得癌癥的治療效果下降。如果能研制出抑制消瘦的藥物,，將對(duì)癌癥患者戰(zhàn)勝病魔大有幫助,。
這項(xiàng)研究成果刊登在最新一期美國《癌癥研究》（Cancer Research）雜志上。
原始出處:
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: [email protected] .
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]
