Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease.
OBJECTIVE
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-alpha 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-alpha 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-alpha 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-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001).


CONCLUSIONS
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.
de Mello
V D F
VD
Department of Clinical Nutrition/Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, P.O. Box 1627, Kuopio, Finland. Vanessa.FerreiradeMello@uku.fi
Lankinen
M
M
Schwab
U
U
Kolehmainen
M
M
Lehto
S
S
Seppänen-Laakso
T
T
Oresic
M
M
Pulkkinen
L
L
Uusitupa
M
M
Erkkilä
A T
AT
D002097:C-Reactive Protein / Q000378:metabolism; D002518:Ceramides / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007511:Ischemia / Q000097:blood / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D009203:Myocardial Infarction / Q000097:blood / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D002518:Ceramides; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein