TY - JOUR
T1 - Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients
T2 - The ColoCare study
AU - Liesenfeld, David B.
AU - Grapov, Dmitry
AU - Fahrmann, Johannes F.
AU - Salou, Mariam
AU - Scherer, Dominique
AU - Toth, Reka
AU - Habermann, Nina
AU - Böhm, Jürgen
AU - Schrotz-King, Petra
AU - Gigic, Biljana
AU - Schneider, Martin
AU - Ulrich, Alexis
AU - Herpel, Esther
AU - Schirmacher, Peter
AU - Fiehn, Oliver
AU - Lampe, Johanna W.
AU - Ulrich, Cornelia M.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Background: Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. Objectives: Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed. Design: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole timeof-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips. Results: Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage. Conclusions: As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.
AB - Background: Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. Objectives: Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed. Design: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole timeof-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips. Results: Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage. Conclusions: As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.
KW - Adipose tissue
KW - Colorectal cancer
KW - Inflammation
KW - Metabolomics
KW - Obesity
KW - Visceral adiposity
UR - http://www.scopus.com/inward/record.url?scp=84938686281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938686281&partnerID=8YFLogxK
U2 - 10.3945/ajcn.114.103804
DO - 10.3945/ajcn.114.103804
M3 - Article
C2 - 26156741
AN - SCOPUS:84938686281
SN - 0002-9165
VL - 102
SP - 433
EP - 443
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 2
ER -