Link between plasma ceramides, inflammation and insulin resistance: Association with serum IL-6 concentration in patients with coronary heart disease

V.D.F. de Mello (Corresponding Author), Maria Lankinen, U. Schwab, M. Kolehmainen, S. Lehto, Tuulikki Seppänen-Laakso, Matej Oresic, L. Pulkkinen, M. Uusitupa, A.T. Erkkilä

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Abstract

Aims/hypothesis: Ceramides and IL-6 have a role in immune–inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-α and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD. Methods: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index). Results: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-α or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-α or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-α had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001). Conclusions/interpretation: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.
Original languageEnglish
Pages (from-to)2612-2615
Number of pages4
JournalDiabetologia
Volume52
Issue number12
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Keywords

  • cardiovascular disease
  • diacylglycerols
  • IL-6
  • inflammation
  • insulin resistance
  • lipidomics

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    de Mello, V. D. F., Lankinen, M., Schwab, U., Kolehmainen, M., Lehto, S., Seppänen-Laakso, T., Oresic, M., Pulkkinen, L., Uusitupa, M., & Erkkilä, A. T. (2009). Link between plasma ceramides, inflammation and insulin resistance: Association with serum IL-6 concentration in patients with coronary heart disease. Diabetologia, 52(12), 2612-2615. https://doi.org/10.1007/s00125-009-1482-9