Altered plasma lysophosphatidylcholines and amides in non-obese and non-diabetic subjects with borderline-to-moderate hypertriglyceridemia: a case-control study

Abstract

Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (CVD). We investigated alterations in plasma metabolites associated with borderline-to-moderate HTG (triglycerides (TG) 150-500 mg/dL). Using UPLC-LTQ-Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non-diabetic and non-obese individuals with borderline-to-moderate HTG were compared with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG, TG <150 mg/dL). When compared to the NTG control group, the HTG group exhibited higher plasma levels of lysophosphatidylcholines (lysoPCs), including C14:0 (q = 0.001) and C16:0 (q = 1.8E-05), and several amides, including N-ethyldodecanamide (q = 2.9E-05), N-propyldodecanamide (q = 3.5E-05), palmitoleamide (q = 2.9E-06), and palmitic amide (q = 0.019). The metabolomic profiles of the HTG group also exhibited lower plasma levels of cis-4-octenedioic acid (q<1.0E-9) and docosanamide (q = 0.002) compared with those of the NTG controls. LysoPC 16:0 and palmitoleamide emerged as the primary metabolites able to discriminate the HTG group from the NTG group in a partial least-squares discriminant analysis and were positively associated with the fasting triglyceride levels. We identified alterations in lysoPCs, amides, and cis-4-octenedioic acid among non-diabetic and non-obese individuals with borderline-to-moderate HTG. These results provide novel insights into the metabolic alterations that occur in the early metabolic stages of HTG. This information may facilitate the design of early interventions to prevent disease progression.

Fig 1. Identification of plasma metabolites in the NTG and HTG groups.

(a) Score scatter plot from the PLS-DA model for the NTG group (n = 111) and HTG group (n = 111). (b) S-plot for the covariance [p] and reliability correlation [p(corr)] from the PLS-DA model.

Fig 2. Correlation matrix of the fasting triglyceride levels, clinical and biochemical parameters, and major plasma metabolites.

The supervised hierarchical clustering plot shows that the 11 most important metabolites stratify the samples according to 15 clinical characteristics. The correlations were obtained by deriving Spearman correlation coefficients. Red represents a positive correlation, and blue represents a negative correlation.