Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice.
Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice.
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DOI：
10.1038/sj.bjc.6603360
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发表时间：
2006-10-23
影响因子：
8.8
通讯作者：
Jenkins, J. R.
中科院分区：
文献类型：
--
作者：
Bing, C.;Russell, S.;Becket, E.;Pope, M.;Tisdale, M. J.;Trayhurn, P.;Jenkins, J. R.
脂肪组织的大量丢失是癌症恶病质的标志，但其细胞和分子基础尚不清楚。本研究检测了携带恶病质诱导肿瘤MAC 16的小鼠的白色脂肪组织的形态学和分子特征。荷瘤小鼠的脂肪组织中含有萎缩的脂肪细胞，其大小不均匀。组织基质中强烈的胶原纤维染色表明纤维化增加。“瘦身”脂肪细胞的超微结构显示严重的脱脂和细胞膜构象的修改。脂肪组织中成脂转录因子（包括CCAAT/增强子结合蛋白α（C/EBPα）、CCAAT/增强子结合蛋白β、过氧化物酶体增殖物激活受体γ和固醇调节元件结合蛋白-1c（SREBP-1c））的mRNA水平显著降低，同时伴有C/EBPα和SREBP-1的蛋白含量降低。SREBP-1c靶点、脂肪酸合成酶、乙酰辅酶A羧化酶、硬脂酰辅酶A去饱和酶1和甘油-3-磷酸酰基转移酶的mRNA水平也下降，葡萄糖转运蛋白-4和瘦素也下降。相反，在荷瘤小鼠的白色脂肪中，过氧化物酶体增殖物激活受体γ共激活因子-1 α和解偶联蛋白-2的mRNA水平增加。这些结果表明，肿瘤诱导的损害的形成和脂肪组织的储存能力发生在小鼠与癌症恶病质。
Extensive loss of adipose tissue is a hallmark of cancer cachexia but the cellular and molecular basis remains unclear. This study has examined morphologic and molecular characteristics of white adipose tissue in mice bearing a cachexia-inducing tumour, MAC16. Adipose tissue from tumour-bearing mice contained shrunken adipocytes that were heterogeneous in size. Increased fibrosis was evident by strong collagen-fibril staining in the tissue matrix. Ultrastructure of ‘slimmed’ adipocytes revealed severe delipidation and modifications in cell membrane conformation. There were major reductions in mRNA levels of adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBPα), CCAAT/enhancer binding protein beta, peroxisome proliferator-activated receptor gamma, and sterol regulatory element binding protein-1c (SREBP-1c) in adipose tissue, which was accompanied by reduced protein content of C/EBPα and SREBP-1. mRNA levels of SREBP-1c targets, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase 1 and glycerol-3-phosphate acyl transferase, also fell as did glucose transporter-4 and leptin. In contrast, mRNA levels of peroxisome proliferators-activated receptor gamma coactivator-1alpha and uncoupling protein-2 were increased in white fat of tumour-bearing mice. These results suggest that the tumour-induced impairment in the formation and lipid storing capacity of adipose tissue occurs in mice with cancer cachexia.
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影响因子：
3.8
作者：
Simons, PJ;van den Pangaart, PS;Boon, L
通讯作者：
Boon, L
影响因子：
3.9
作者：
Horton, JD
通讯作者：
Horton, JD
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64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM
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168.9
作者：
Bastard, JP;Caron, M;Capeau, J
通讯作者：
Capeau, J
影响因子：
4.7
作者：
Bing, C;Taylor, S;Williams, G
通讯作者：
Williams, G