Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients

The ColoCare study

David B. Liesenfeld, Dmitry Grapov, Johannes F. Fahrmann, Mariam Salou, Dominique Scherer, Reka Toth, Nina Habermann, Jürgen Böhm, Petra Schrotz-King, Biljana Gigic, Martin Schneider, Alexis Ulrich, Esther Herpel, Peter Schirmacher, Oliver Fiehn, Johanna W. Lampe, Cornelia M. Ulrich

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)433-443
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume102
Issue number2
DOIs
StatePublished - Aug 1 2015

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Metabolomics
Intra-Abdominal Fat
Subcutaneous Fat
Colorectal Neoplasms
Adipose Tissue
Mass Spectrometry
Neoplasms
Serum
Plasmalogens
Lipids
Gene Expression
Metabolome
Sphingomyelins
Phospholipases
Adiposity
Gene Expression Profiling
Enzymes
Lipid Metabolism
Arachidonic Acid
Liquid Chromatography

Keywords

  • Adipose tissue
  • Colorectal cancer
  • Inflammation
  • Metabolomics
  • Obesity
  • Visceral adiposity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients : The ColoCare study. / Liesenfeld, David B.; Grapov, Dmitry; Fahrmann, Johannes F.; Salou, Mariam; Scherer, Dominique; Toth, Reka; Habermann, Nina; Böhm, Jürgen; Schrotz-King, Petra; Gigic, Biljana; Schneider, Martin; Ulrich, Alexis; Herpel, Esther; Schirmacher, Peter; Fiehn, Oliver; Lampe, Johanna W.; Ulrich, Cornelia M.

In: American Journal of Clinical Nutrition, Vol. 102, No. 2, 01.08.2015, p. 433-443.

Research output: Contribution to journalArticle

Liesenfeld, DB, Grapov, D, Fahrmann, JF, Salou, M, Scherer, D, Toth, R, Habermann, N, Böhm, J, Schrotz-King, P, Gigic, B, Schneider, M, Ulrich, A, Herpel, E, Schirmacher, P, Fiehn, O, Lampe, JW & Ulrich, CM 2015, 'Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: The ColoCare study', American Journal of Clinical Nutrition, vol. 102, no. 2, pp. 433-443. https://doi.org/10.3945/ajcn.114.103804
Liesenfeld, David B. ; Grapov, Dmitry ; Fahrmann, Johannes F. ; Salou, Mariam ; Scherer, Dominique ; Toth, Reka ; Habermann, Nina ; Böhm, Jürgen ; Schrotz-King, Petra ; Gigic, Biljana ; Schneider, Martin ; Ulrich, Alexis ; Herpel, Esther ; Schirmacher, Peter ; Fiehn, Oliver ; Lampe, Johanna W. ; Ulrich, Cornelia M. / Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients : The ColoCare study. In: American Journal of Clinical Nutrition. 2015 ; Vol. 102, No. 2. pp. 433-443.
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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.

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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.

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KW - Adipose tissue

KW - Colorectal cancer

KW - Inflammation

KW - Metabolomics

KW - Obesity

KW - Visceral adiposity

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