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Adipose tissue pathways involved in weight loss of cancer cachexia
- Source :
- British Journal of Cancer, British Journal of Cancer; Vol 102
- Publication Year :
- 2010
- Publisher :
- Nature Publishing Group, 2010.
-
Abstract
- 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.
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Cachexia
extracellular matrix
wasting
Adipose tissue
Gene Expression
Biology
Extracellular matrix
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Weight loss
Adipocyte
Internal medicine
Neoplasms
Gene expression
Weight Loss
medicine
Humans
Obesity
Cell adhesion
Molecular Diagnostics
030304 developmental biology
Aged
Oligonucleotide Array Sequence Analysis
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
cellular adhesion
medicine.disease
Actin cytoskeleton
adipose tissue
Endocrinology
Oncology
chemistry
Gene Expression Regulation
030220 oncology & carcinogenesis
Female
medicine.symptom
microarray
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15321827 and 00070920
- Volume :
- 102
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....8e60b3160b084ce4f28607d3013b35a3