Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia
Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia
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DOI：
10.1530/joe-12-0307
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Seelaender, M.
中科院分区：
文献类型：
--
作者：
Batista, M. L., Jr.;Neves, R. X.;Seelaender, M.
癌症恶病质诱导脂肪量的减少，这是在人类和动物模型中观察到的显著体重减轻的很大一部分；然而，文献并没有提供一致的信息，关于体重减轻的设定值和不同的内脏脂肪组织库是如何促成这种症状的。为了评估这一点，8周龄雄性Wistar大鼠皮下接种1 ml （2 × 10(7)）肿瘤细胞（Walker 256）。在第0、4、7和14天收集不同内脏白色脂肪组织（WAT）库的样本，在-80℃保存（每组每天7 ~ 10只）。与第0天相比，第14天肠系膜和腹膜后储库质量下降最大。PPAR γ (2) （PPARG）基因和蛋白表达在所有三个脂肪组织库中肿瘤植入后显著下降，而C/EBP α (CEBPA)和SREBP-1c （SREBF1）表达随时间下降仅在附睾和腹膜后库中。脂肪生成基因表达的降低和内脏WAT的形态破坏进一步得到了periilipin mRNA和蛋白水平的显著降低的支持。WAT中炎症和巨噬细胞浸润的经典标志物（f4/80、CD68和MIF-1 α）在恶病质晚期显著升高（尽管在恶病质过程中呈增量模式），并呈现位点特异性调控。这些结果表明，脂肪组织脂质储存功能的损害发生在不同的时间，并且在癌症恶病质进展过程中，肠系膜脂肪组织比其他内脏脂肪组织更能抵抗“减脂作用”。内分泌学杂志（2012）215,363 -373
Cancer cachexia induces loss of fat mass that accounts for a large part of the dramatic weight loss observed both in humans and in animal models; however, the literature does not provide consistent information regarding the set point of weight loss and how the different visceral adipose tissue depots contribute to this symptom. To evaluate that, 8-week-old male Wistar rats were subcutaneously inoculated with 1 ml (2 x 10(7)) of tumour cells (Walker 256). Samples of different visceral white adipose tissue (WAT) depots were collected at days 0, 4, 7 and 14 and stored at -80 degrees C (seven to ten animals/each day per group). Mesenteric and retroperitoneal depot mass was decreased to the greatest extent on day 14 compared with day 0. Gene and protein expression of PPAR gamma(2) (PPARG) fell significantly following tumour implantation in all three adipose tissue depots while C/EBP alpha (CEBPA) and SREBP-1c (SREBF1) expression decreased over time only in epididymal and retroperitoneal depots. Decreased adipogenic gene expression and morphological disruption of visceral WAT are further supported by the dramatic reduction in mRNA and protein levels of perilipin. Classical markers of inflammation and macrophage infiltration (f4/80, CD68 and MIF-1 alpha) in WAT were significantly increased in the later stage of cachexia (although showing a incremental pattern along the course of cachexia) and presented a depot-specific regulation. These results indicate that impairment in the lipid-storing function of adipose tissue occurs at different times and that the mesenteric adipose tissue is more resistant to the 'fat-reducing effect' than the other visceral depots during cancer cachexia progression. Journal of Endocrinology (2012) 215, 363-373