Serum Metabolomic Signatures of Dyslipidemia in Narcolepsy Type 1: A Multi-Center Cross-Sectional Study

We aimed to explore the candidate metabolic pathways involved in narcolepsy type 1 (NT1)-related dyslipidemia.

Forty-four patients with NT1, and 44 controls were included in this multicenter metabolomics study. All participants included underwent an overnight polysomnography and multiple sleep latency test. Fasting blood samples were collected to assess lipid levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). Serum metabolomics was used to explore characteristic metabolites in the discovery and validation sets.

Patients with NT1 had higher values for TC (5.13 ± 0.14 vs 4.63 ± 0.14 mmol/L, P = 0.024), and LDL-C (3.01±0.13 vs 2.59 ± 0.13 mmol/L, P = 0.038), but a lower HDL-C (1.32 ± 0.07 vs 1.53 ± 0.07 mmol/L, P = 0.039) compared to controls after adjusting for potential confounders. Enrichment analysis suggested that arginine biosynthesis and arginine and proline metabolism were different between patients with NT1 and controls. Four NT1-related metabolites were identified, glutamate (β = -0.319, P = 0.049) correlated negatively with HDL-C, after adjusting for potential confounders.

Increased serum glutamate level is associated with decreased level of HDL-C in patients with NT1. Arginine metabolism dysfunction may contribute to dyslipidemia in NT1.