Dick C. Chan

Background: Obesity is associated with adverse alterations in lipoprotein profiles and increased cardiometabolic risk, yet standard clinical lipid measures provide limited resolution of the underlying lipoprotein structure. Here, we perform a population-level characterisation of the impact of obesity on the high-resolution blood lipoprotein subfraction profile. Methods: Lipoprotein profiles were investigated in an Australian cohort ( n = 1806) stratified by Body Mass Index (BMI) (healthy weight, overweight, obese). The composition and particle number of lipoproteins and their subfractions were quantified ( n = 112 parameters) using ¹ H NMR spectroscopy. Associations between BMI, lipoprotein subfractions, and particle number ratios were evaluated. Key BMI-associated ratios were validated in a second Australian cohort ( n = 1313) Results: Participants with obesity had significantly higher particle concentrations of VLDL and IDL and lower HDLs, while total LDL concentration was similar between the BMI categories. Notably, obesity was associated with a marked redistribution of LDL subfractions, with a shift from larger, buoyant LDL1–3 particles to smaller, dense LDL4–6 particles, accompanied by a similar shift in HDL subfractions, with proportionally lower concentrations of HDL1–3 particles in the high BMI group. An inverse association between BMI was found for two LDL particle number ratios (LDL1–3:LDL4–6 and LDL2:LDL5) and one HDL ratio (HDL1:HDL4), which demonstrated good discriminatory power for obesity status (AUROCs 0.70–0.74). Conclusions: The pattern of lipoprotein subfraction redistribution in participants with obesity was consistent across cohorts. These subfractional changes offer enhanced resolution compared with conventional lipid and lipoprotein measures and may contribute to improved cardiovascular risk stratification in individuals with obesity.