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Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer.

ABSTRACT: 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.

SUBMITTER: Haffa M

PROVIDER: S-EPMC6763280 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer.

Haffa Mariam M Holowatyj Andreana N AN Kratz Mario M Toth Reka R Benner Axel A Gigic Biljana B Habermann Nina N Schrotz-King Petra P Böhm Jürgen J Brenner Hermann H Schneider Martin M Ulrich Alexis A Herpel Esther E Schirmacher Peter P Straub Beate K BK Nattenmüller Johanna J Kauczor Hans-Ulrich HU Lin Tengda T Ball Claudia R CR Ulrich Cornelia M CM Glimm Hanno H Scherer Dominique D

The Journal of clinical endocrinology and metabolism 20191101 11

<h4>Context</h4>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.<h4>Objective</h4>We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of d ...[more]

PMID: 31225875

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Project description:Adipose tissue (AT) is an endocrine organ with a central role on whole-body energy metabolism and development of metabolic diseases. Single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq, respectively) analyses in mice and human AT have revealed vast cell heterogeneity and functionally distinct subtypes that are potential therapeutic targets to metabolic disease. In periparturient dairy cows, AT goes through intensive remodeling and its dysfunction is associated with metabolic disease pathogenesis and decreased productive performance. The contributions of depot-specific cells and subtypes to the development of diseases in dairy cows remain to be studied. Our objective was to elucidate differences in cellular diversity of visceral (VAT) and subcutaneous (SAT) AT in dairy cows at the single-nuclei level. We collected matched SAT and VAT samples from three dairy cows and performed snRNA-seq analysis. We identified distinct cell types including four major mature adipocytes (AD) and three stem and progenitor cells (ASPC) subtypes, along with endothelial cells (EC), mesothelial cells (ME), immune cells, and pericytes and smooth muscle cells. All major cell types were present in both SAT and VAT, although a strong VAT-specificity was observed for ME, which were basically absent in SAT. One ASPC subtype was defined as adipogenic (PPARG+) while the other two had a fibro-adipogenic profile (PDGFRA+). We identified vascular and lymphatic EC subtypes, and different immune cell types and subtypes in both SAT and VAT, i.e., macrophages, monocytes, T cells, and natural killer cells. Not only did VAT show a greater proportion of immune cells, but these visceral immune cells had greater activation of pathways related to immune and inflammatory response, and complement cascade in comparison with SAT. There was a substantial contrast between depots for gene expression of complement cascade, which were greatly expressed by VAT cell subtypes compared to SAT, indicating a pro-inflammatory profile in VAT. Unprecedently, our study demonstrated cell-type and depot-specific heterogeneity in VAT and SAT of dairy cows. A better understanding of depot-specific molecular and cellular features of SAT and VAT will aid in the development of AT-targeted strategies to prevent and treat metabolic disease in dairy cows, especially during the periparturient period.

Dataset Information

Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer.

Publications

Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer.

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