Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer
| Autor: | Mariam Haffa, Martin Schneider, Claudia R. Ball, Nina Habermann, Tengda Lin, Johanna Nattenmüller, Cornelia M. Ulrich, Biljana Gigic, Beate K. Straub, Esther Herpel, Axel Benner, Hanno Glimm, Reka Toth, Alexis Ulrich, Jürgen Böhm, Hans-Ulrich Kauczor, Dominique Scherer, Petra Schrotz-King, Peter Schirmacher, Andreana N. Holowatyj, Hermann Brenner, Mario Kratz |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Subcutaneous Fat Adipose tissue Context (language use) Intra-Abdominal Fat Biology Biochemistry Energy homeostasis Transcriptome Endocrinology Internal medicine medicine Humans Clinical Research Articles Aged Inflammation Regulation of gene expression Gene Expression Profiling Biochemistry (medical) nutritional and metabolic diseases Cancer Lipid metabolism Middle Aged Lipid Metabolism medicine.disease Gene Expression Regulation Neoplastic Gene expression profiling Female Colorectal Neoplasms |
| Zdroj: | J Clin Endocrinol Metab |
| ISSN: | 1945-7197 0021-972X |
| Popis: | Context Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking. Objective We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression. Design Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT. Results VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism–related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression. Conclusions This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass–associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer. |
| Databáze: | OpenAIRE |
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