Serum lysophospholipidome of dietary origin as a suitable susceptibility/risk biomarker of human hypercholesterolemia: A cross-sectional study

Abstract

Background & aims: Whether bioactive lysophospholipids (lyso-PLs) and trimethylamine-N-oxide (TMAO) serve as non-invasive biomarkers in early human hypercholesterolemia (HC) is unknown. The present work aimed at assessing whether serum lyso-PLs and plasma TMAO may be suitable susceptibility/risk biomarkers of HC in humans. Secondarily, we aimed to evaluate the relationships between targeted metabolites with diet composition and circulating liver transaminases, and verified the results in hamsters. Methods: A targeted metabolomics approach determined serum TMAO and plasma lysophosphatidylcholines (lyso-PCs) and lysophosphatidylethanolamines (lyso-PEs) in the serum of 70 low (L-LDL-c) and 48 moderate to high (MH-LDL-c) LDL-cholesterol subjects. Additionally, the relationships between targeted metabolites, liver transaminases and diet, especially fatty acids (FAs) intake, were tested. In parallel, plasma and liver lyso-PLs profile was studied in 16 hamsters fed a moderate high-fat (HFD) or low-fat (LFD) diet for 30 days. Results: The predictive models pointed lyso-PC15:0 and lyso-PE18:2 as the most discriminant lyso-PLs among groups. In MH-LDL-c, LDL-cholesterol and saturated FAs were positively associated with lyso-PC15:0, whereas in L-LDL-c, LDL-cholesterol and polyunsaturated FAs (PUFAs) were negatively and positively related with lyso-PE18:2, respectively. Interestingly, in MH-LDL-c, the lower lyso-PE 18:2 concentrations were indicative of LDL-cholesterol increase. The results in HFD-fed hamsters showed higher intrahepatic accumulation of lyso-PLs-containing essential n-6 PUFAs, including lyso-PE18:2, than LFD-fed hamsters. Conclusions: Overall, these results reveal a possible hepatic adaptive mechanism to counteract dietinduced steatosis in animal and hypercholesterolemia progression in human. Particularly, low serum lyso-PE 18:2 suggest a suitable susceptibility/risk biomarker of HC in humans.

Metabolic profiles reflect weight loss maintenance and the composition of diet after very-low-energy diet

“…Circulating metabolites act as signalling molecules and intermediates of glucose, lipid, and amino acid metabolisms participating in multiple molecular pathways related to health and disease [7]. For example, alterations in certain plasma metabolite levels have been considered biomarkers of cardiometabolic disease risk [8,9] and impairments or improvements in glucose and lipid metabolism [10,11]. Dietary patterns [12,13] and foods [14] affect the metabolome.…”