Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients : the ColoCare study

© 2015 American Society for Nutrition..

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 time-of-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.

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:102

Enthalten in:

The American journal of clinical nutrition - 102(2015), 2 vom: 09. Aug., Seite 433-43

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Adipose tissue
Biomarkers
Clinical Trial
Colorectal cancer
Inflammation
Journal Article
Metabolomics
Obesity
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Visceral adiposity

Anmerkungen:

Date Completed 19.10.2015

Date Revised 18.03.2023

published: Print-Electronic

ClinicalTrials.gov: NCT02328677

Citation Status MEDLINE

doi:

10.3945/ajcn.114.103804

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM250709074