The high‐density lipoprotein lipidome in metabolic syndrome: A systematic review

Background Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including low high‐density lipoprotein cholesterol (HDL‐C) levels. Although HDL‐C is an established cardiovascular biomarker, in MetS this marker captures only a fraction of the profound alterations occurring within HDL particles. The cardiometabolic role of HDLs in MetS remains insufficiently understood because the functional properties and molecular components of HDLs, rather than HDL‐C alone, are likely key determinants of cardiovascular risk. Since the early 2000s, research has revealed that HDL particles comprise over 280 proteins and more than 300 lipid species, underscoring their biological complexity. Moreover, HDL composition and function are extensively remodelled in MetS, highlighting the importance of characterising the differences in HDL composition between health and disease. In this systematic review, we aimed to examine differences in the HDL lipidome between MetS patients and healthy controls. Methods A comprehensive literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. The PRISMA guidelines for systematic reviews were followed, and four records met the eligibility criteria. Results Overall, the HDL lipidome was markedly different in MetS compared with healthy individuals. MetS was consistently associated with higher levels of triacylglycerides (TAGs) and phosphatidylinositol, alongside lower levels of several key lipid families, indicating a broad remodelling of HDL composition. Conclusions These findings indicate that the HDL lipidome is substantially altered in MetS, with potential consequences for HDL functionality. Although the mechanistic implications remain to be fully elucidated, TAG enrichment may contribute to lower HDL levels and changes in HDL surface lipids may impair essential functions such as cholesterol efflux. Further studies are needed to validate these patterns and determine their impact on HDL function and cardiometabolic risk.