Adipose tissue pathways involved in weight loss of cancer cachexia

被引：106

作者：

Dahlman, I. ^{[1
]}

Mejhert, N. ^{[1
]}

Linder, K. ^{[1
]}

Agustsson, T. ^{[2
]}

Mutch, D. M. ^{[3
]}

Kulyte, A. ^{[1
]}

Isaksson, B. ^{[2
]}

Permert, J. ^{[2
]}

Petrovic, N. ^{[4
]}

Nedergaard, J. ^{[4
]}

Sjoelin, E. ^{[1
]}

Brodin, D. ^{[5
]}

Clement, K. ^{[6
,7
,8
]}

Dahlman-Wright, K. ^{[5
]}

Ryden, M. ^{[1
]}

Arner, P. ^{[1
]}

机构：

[1] Karolinska Inst, Karolinska Univ Hosp, Dept Med, SE-14186 Stockholm, Sweden

[2] Karolinska Inst, Karolinska Univ Hosp, Dept Surg, SE-14186 Stockholm, Sweden

[3] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada

[4] Stockholm Univ, Wenner Gren Inst, Arrhenius Labs F3, SE-10691 Stockholm, Sweden

[5] Karolinska Inst, Dept Biosci & Nutr, SE-14186 Stockholm, Sweden

[6] INSERM, U872, Nutr Team 7, F-75006 Paris, France

[7] Univ Paris 06, Cordeliers Res Ctr, F-75006 Paris, France

[8] Hop La Pitie Salpetriere, AP HP, F-75013 Paris, France

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 102卷 / 10期

关键词：

adipose tissue; wasting; microarray; cellular adhesion; extracellular matrix; EXTRACELLULAR-MATRIX; GENE ONTOLOGY; CELL-DEATH; EXPRESSION; INFLAMMATION; METABOLISM; LIPOLYSIS; OBESITY; BIOPSY; ACID;

D O I：

10.1038/sj.bjc.6605665

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. METHODS: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n = 13) or without (n = 14) cachexia. RESULTS: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia. CONCLUSIONS: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin. British Journal of Cancer (2010) 102, 1541-1548. doi:10.1038/sj.bjc.6605665 www.bjcancer.com Published online 20 April 2010 (C) 2010 Cancer Research UK

引用

页码：1541 / 1548

页数：8

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