Transcriptome profiling of adipose tissue reveals depot-specific metabolic alterations among colorectal cancer patients.

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 cancer patients are lacking. OBJECTIVE We compared transcriptome profiles of visceral (VAT) and subcutaneous (SAT) adipose tissue from colorectal cancer patients, 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 computed tomography. RESULTS VAT compared to 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. 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 colorectal cancer patients.