Associations of Plasma Lipidomic Profiles with Uric Acid and Hyperuricemia Risk in Middle-Aged and Elderly Chinese

Abstract

AbstractLittle is known about the links of disturbed lipid metabolism with hyperuricemia (HUA). We aimed to investigate the associations of lipidomic profiles with uric acid (UA)/HUA and their modifying factors in middle-aged and elderly Chinese. A total of 350 lipids were quantified in 2247 community-based Chinese aged 50–70 years by high-coverage targeted lipidomics. HUA was defined by plasma UA > 420 μmol/L in men or > 360 μmol/L in women. The prevalence of HUA in this population was 10.4%. After multivariable adjustment including BMI and lifestyle, 123 lipids were significantly associated with UA, predominantly glycerolipids (GLs) and glycerophospholipids (GPs). Specifically, diacylglycerol [DAG (16:0/22:5), DAG (16:0/22:6), DAG (18:1/20:5), DAG (18:1/22:6)], phosphatidylcholine [PC (16:0/20:5)), and triacylglycerol (TAG (53:0)] were the most significant lipid signatures positively associated with HUA risk, while lysophosphatidylcholine (LPC (20:2)) was inversely associated with HUA risk (p < 0.05). Network analysis also showed a positive association between TAGs/PCs/DAGs contained module and HUA risk (p < 0.01). Notably, HUA-related lipids were associated with de novo lipogenesis fatty acids, especially 16:1n-7 (Spearman correlation coefficients = 0.32–0.41, p < 0.001). Reduced rank regression showed that increased aquatic products intake was correlated to elevated HUA risk and HUA-associated lipids; while high dairy consumption was correlated with low level of HUA-associated lipids (|factor loadings| ≥ 0.2). Moreover, mediation analyses suggested that the lipid-HUA associations were partially mediated by retinol-binding protein 4 (RBP4, mediation proportion 5–14%), an adipokine linked with dyslipidemia and insulin resistance. In conclusion, disturbed specific metabolisms of GLs and GPs were associated with high prevalent HUA, partially mediated by RBP4 and/or influenced by certain dietary factors.