Dynamic lipidome alterations associated with human health, disease and ageing

TLDR

Lipids originate endogenously or exogenously and influence cell membranes, energy metabolism, and signaling. The study profiled over 1,500 plasma samples from 112 participants across up to nine years to characterize the physiological roles of diverse lipid subclasses. Longitudinal profiling identified more than 800 lipid species linked to diabetes, ageing, and inflammation, revealed dynamic lipidome changes during viral infection and insulin resistance that affect immune homeostasis, and highlighted accelerated subclass alterations in insulin‑resistant individuals, providing personalized insights for monitoring and intervention.

Abstract

Abstract Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management and cellular signalling. Here, we report >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation, as well as cytokine–lipidome networks. We performed comprehensive longitudinal lipidomic profiling and analysed >1,500 plasma samples from 112 participants followed for up to 9 years (average 3.2 years) to define the distinct physiological roles of complex lipid subclasses, including large and small triacylglycerols, ester- and ether-linked phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, cholesterol esters and ceramides. Our findings reveal dynamic changes in the plasma lipidome during respiratory viral infection, insulin resistance and ageing, suggesting that lipids may have roles in immune homoeostasis and inflammation regulation. Individuals with insulin resistance exhibit disturbed immune homoeostasis, altered associations between lipids and clinical markers, and accelerated changes in specific lipid subclasses during ageing. Our dataset based on longitudinal deep lipidome profiling offers insights into personalized ageing, metabolic health and inflammation, potentially guiding future monitoring and intervention strategies.