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  • Original Article
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Adipocyte and Cell Biology

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women

International Journal of Obesity volume 40, pages 706–713 (2016)Cite this article

Subjects

Abstract

Aims:

The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance.

Methods:

Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed.

Results:

In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.

Interpretation:

The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.

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Acknowledgements

We are grateful to the women who participated in this study. The study was supported by a Diabetes Australia Research Trust (DART) Award, the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC IRIISS. JMW takes full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript.

Author contributions

This study was designed by JMW, LCH, PEO and PM. JMW, GN, KN, CB, JW and MC performed the experiments. GKS and RL analysed the microarray data. JMW collated and analysed the results and drafted the manuscript. All authors edited the manuscript and approved it for submission.

Author information

Author notes

  1. P J Meikle and L C Harrison: Joint senior authors.

Authors and Affiliations

  1. Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    J M Wentworth, G Naselli, K Ngui & L C Harrison

  2. Monash University Centre for Obesity Research and Education, Melbourne, Victoria, Australia

    J M Wentworth & P E O'Brien

  3. Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    G K Smyth & R Liu

  4. Department of Mathematics and Statistics, University of Melbourne, Carlton, Victoria, Australia

    G K Smyth

  5. Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia

    C Bruce

  6. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    J Weir, M Cinel & P J Meikle

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  1. J M Wentworth
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Corresponding author

Correspondence to J M Wentworth.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Wentworth, J., Naselli, G., Ngui, K. et al. GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women. Int J Obes 40, 706–713 (2016). https://doi.org/10.1038/ijo.2015.223

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