Obesity rather than regional fat depots marks the metabolomic pattern of adipose tissue: An untargeted metabolomic approach

Authors

  • F.A. Hanzu,

    Corresponding author
    1. Department of Endocrinology and Nutrition, Diabetes and Obesity Research Laboratory, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
    2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
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  • M. Vinaixa,

    1. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
    2. Center for Omic Sciences, Universitat Rovira i Virgili, Tarragona, Spain
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  • A. Papageorgiou,

    1. Department of Endocrinology and Nutrition, Diabetes and Obesity Research Laboratory, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
    2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
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  • M. Párrizas,

    1. Department of Endocrinology and Nutrition, Diabetes and Obesity Research Laboratory, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
    2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
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  • X. Correig,

    1. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
    2. Center for Omic Sciences, Universitat Rovira i Virgili, Tarragona, Spain
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  • S. Delgado,

    1. Department of Gastrointestinal Surgery, Hospital Clínic de Barcelona, Spain
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  • F. Carmona,

    1. Department of Gynecology and Obstetrics, Hospital Clínic de Barcelona, IDIBAPS, Spain
    2. Faculty of Medicine, University of Barcelona, Spain
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  • S. Samino,

    1. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
    2. Center for Omic Sciences, Universitat Rovira i Virgili, Tarragona, Spain
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  • J. Vidal,

    1. Department of Endocrinology and Nutrition, Diabetes and Obesity Research Laboratory, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
    2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
    3. Faculty of Medicine, University of Barcelona, Spain
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  • R. Gomis

    1. Department of Endocrinology and Nutrition, Diabetes and Obesity Research Laboratory, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
    2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
    3. Faculty of Medicine, University of Barcelona, Spain
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  • Funding agencies: Supported by grants from the Ministerio de Educacion y Ciencia (SAF 2010/19527), Generalitat de Catalunya (SGR2009/1426), CIBERDEM (Centro de Investigación en Redes de Diabetes y Enfermedades Metabolicas), an initiative of the Instituto de Salud Carlos III, and the Ist Award Boston Scientific of the Sociedad Espanola de Diabetes 2009. FAH was a recipient of a Rio-Hortega contract from the Instituto de Salud Carlos III (ISCIII, Spain) and KP a recipient of an IDIBAPS fellowship.

  • Disclosure: The authors declare no conflict of interest.

  • Author contributions: MV, SS, and AP designed and carried out experiments. MV, MP, XC designed experiments and carried out the analysis. JV, RG, SD, and FC designed procedures for patient recruitment, clinical phenotyping and analysis. FAH was involved in all steps of the study. All authors were involved in writing the article and had final approval of the submitted and published versions.

Abstract

Objective

This study compares the patterns of visceral (VIS) and subcutaneous (SC) adipose tissue (AT)-derived metabolites from non-obese (BMI 24-26 kg/m2) and obese subjects (BMI > 40 kg/m2) with no major metabolic risk factors other than BMI.

Methods

SC- and VIS- AT obtained from obese (Ob) and non-obese (NOb) subjects during surgery were incubated to obtain their metabolites. Differences related to obesity or anatomical provenances of AT were assessed using an untargeted metabolomics approach based on gas chromatography-mass spectrometry.

Results

The overall effect of obesity on the metabolite profile resulted more remarkable than the effect of regional AT. Only the depletion of 2-ketoisocaproic (2-KIC) acid reached statistical significance for the SC-AT alone, although it was observed in both depots. Obesity induced more significant changes in several amino acids levels of the VIS-AT metabolites. On the one hand, higher released levels of glutamine and alanine were detected in the VIS- obese AT, whereas on the other, the VIS- obese AT presented a diminished uptake of essential amino acids (methionine, threonine, lysine), BCAAs, leucine, and serine.

Conclusion

This study shows that obesity markedly affects the amino acid metabolic signature of the AT before the clinical onset of other significant metabolic alterations aside from BMI.

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