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Physiology

Plasma lipid profiling of tissue-specific insulin resistance in human obesity

International Journal of Obesity volume 43, pages 989–998 (2019)Cite this article

Subjects

Abstract

Background/Objectives

Obesity-associated insulin resistance (IR) may develop in multiple organs, representing different aetiologies towards cardiometabolic diseases. This study aimed to identify distinct plasma lipid profiles in overweight/obese individuals who show muscle-IR and/or liver-IR.

Subjects/Methods

Baseline data of the European multicenter DiOGenes project were used (n = 640; 401 women, nondiabetic BMI: 27-45 kg/m2). Muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI) were derived from a 5-point oral glucose tolerance test. The 140 plasma lipids were quantified by liquid chromatography–mass spectrometry. Linear mixed models were used to evaluate associations between MISI, HIRI and plasma lipids.

Results

MISI was comparable between sexes while HIRI and triacylglycerol (TAG) levels were lower in women than in men. MISI was associated with higher lysophosphatidylcholine (LPC) levels (standardized (std)β = 0.126; FDR-p = 0.032). Sex interactions were observed for associations between HIRI, TAG and diacylglycerol (DAG) lipid classes. In women, but not in men, HIRI was associated with higher levels of TAG (44 out of 55 species) and both DAG species (stdβ: 0.139–0.313; FDR-p < 0.05), a lower odd-chain/even-chain TAG ratio (stdβ = −0.182; FDR-p = 0.005) and a lower very-long-chain/long-chain TAG ratio (stdβ = −0.156; FDR-p = 0.037).

Conclusions

In overweight/obese individuals, muscle insulin sensitivity is associated with higher plasma LPC concentrations. Women have less hepatic IR and lower TAG than men. Nevertheless, hepatic IR is associated with higher plasma TAG and DAG concentrations and a lower abundance of odd-chain and very-long-chain TAG in women, but not in men. This suggests a more pronounced worsening of plasma lipid profile in women with the progression of hepatic IR.

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Author contributions

WHMS and AA designed the DiOGenes clinical study; AV, AA, WHMS and TH designed the lipidomics studies; EEB designed and led the present study; NV and BWvdK conducted the statistical analyses; JWEJ, NV and MMJvG supervised the lipidomics data analyses; BWvdK wrote the manuscript. All authors contributed to revising the article critically for important intellectual content and gave their final approval of the version to be published. EEB is the guarantor of this work.

Funding

This study was supported by the European Commission, Food Quality and Safety Priority of the Sixth Framework Program (FP6-2005-513946), through a grant from the Maastricht University Medical Center and Nestlé Institute of Health Sciences, Lausanne, Switzerland.

Author information

Authors and Affiliations

  1. Department of Human Biology and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands

    Birgitta W. van der Kolk, Nicole Vogelzangs, Johan W. E. Jocken, Wim H. M. Saris & Ellen E. Blaak

  2. Department of Epidemiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Nicole Vogelzangs & Ilja C. W. Arts

  3. Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands

    Nicole Vogelzangs & Ilja C. W. Arts

  4. Nestlé Institute of Health Sciences, Lausanne, Switzerland

    Armand Valsesia

  5. Netherlands Metabolomics Centre, Leiden, The Netherlands

    Thomas Hankemeier

  6. Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark

    Arne Astrup

  7. Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands

    Marleen M. J. van Greevenbroek

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  1. Birgitta W. van der Kolk
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the DiOGenes consortium

Corresponding author

Correspondence to Birgitta W. van der Kolk.

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Conflict of interest

AV is a full-time employee at Nestlé Institute of Health Sciences SA. WHMS reports having received research support from several food companies such as Nestlé, DSM, Unilever, Nutrition et Sante and Danone as well as Pharmaceutical companies such as GSK, Novartis and Novo Nordisk; he is an unpaid scientific advisor for the International Life Science Institute, ILSI Europe. AA reports grants and personal fees from Global Dairy Platform, personal fees from McCain Foods, McDonald’s, Arena Pharmaceuticals Inc., Basic Research, Dutch Beer Knowledge Institute, Netherlands, Gelesis, Novo Nordisk, Denmark, Orexigen Therapeutics Inc., S-Biotek, Denmark, Twinlab and Vivus Inc., grants from Arla Foods, Denmark, Danish Dairy Research Council and Nordea Foundation, Denmark, outside the submitted work, and royalties received for the book first published in Danish as 'Verdens Bedste Kur' (Politiken; Copenhagen, Denmark), and subsequently published in Dutch as 'Het beste dieet ter wereld' (Kosmos Uitgevers; Utrecht/Antwerpen, Netherlands), in Spanish as 'Plan DIOGENES para el control del peso. La dieta personalizada inteligente' (Editorial Evergra ́ficas; Léon, Spain) and in English as 'World’s Best Diet' (Penguin, Australia). EEB receives grant support from food industry such as DSM, Danone, Friesland Campina, Avebe and Sensus, partly within the context of public–private consortia and has received funding from pharmaceutical companies like Novartis. She is involved in several task forces/expert groups related to the International Life Science Institute, ILSI Europe.

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van der Kolk, B.W., Vogelzangs, N., Jocken, J.W.E. et al. Plasma lipid profiling of tissue-specific insulin resistance in human obesity. Int J Obes 43, 989–998 (2019). https://doi.org/10.1038/s41366-018-0189-8

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