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.
Highlights
Hypertriglyceridemia (HTG) is a polygenic and environmentally determined metabolic disease that affects the production and clearance of triglyceride (TG)-rich lipoproteins [1]
There was no significant difference in LDL-cholesterol between the HTG and NTG groups, higher ox-LDL levels were observed in the HTG group and were positively correlated with the fasting TG levels, lysoPCs containing C14:0, C16:0, and C18:0, and primary fatty acid amides such as palmitoleamide, palmitic amide, and oleamide
The HTG group exhibited a significant increase in the fasting Free fatty acid (FFA) and FFA response area, which were positively and independently correlated with the fasting TG levels. These results suggest that alterations in the plasma fatty acid amides may reflect changes in their respective fatty acids in the HTG group
Summary
Hypertriglyceridemia (HTG) is a polygenic and environmentally determined metabolic disease that affects the production and clearance of triglyceride (TG)-rich lipoproteins [1]. An elevated level of plasma TG is an independent risk factor for type 2 diabetes (T2D), metabolic syndrome, and atherosclerotic cardiovascular disease (CVD) [2, 3], with a prevalence of up to 30– 50% in these populations. Many studies have focused on the loci of genetic susceptibility [1] of HTG and its co-morbidity with several metabolic diseases, including obesity, T2D, and CVD. Borderline-to-moderate HTG-induced perturbations in metabolism have not been characterized among non-diabetic and non-obese individuals. Studies are needed to determine the role of altered plasma metabolic profiles in individuals who only have borderline-to-moderate HTG and do not have diabetes or obesity. The main aim of this study was to identify metabolic changes associated with borderline-to-moderate HTG levels in non-obese and non-diabetic individuals to uncover new insights regarding early metabolic perturbations associated with elevated TG levels
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