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Peer-reviewedCC BY 4.0International Journal of Obesity (2005)

High resolution lipoprotein subfraction profiling identifies obesity associated distributional changes in LDL and HDL subfractions and particle ratios

  • Novia Minaee1
  • Reika Masuda1
  • Philipp Nitschke1
  • Drew Hall1
  • Jennie Hui2,3
  • Michael L. Hunter2,4
  • Leon Flicker5
  • Graeme J. Hankey5,6
  • Osvaldo P. Almeida5,7,8
  • Dick C. Chan5
  • Gerald F. Watts5,9
  • Muhammad Saeed Ahmad10,11
12 more authors
  • Huda M. Alkreathy11,12
  • Zoheir Abdullah Dhamanouri11,12
  • Hartmut Schäfer13
  • Manfred Spraul13
  • Claire Cannet13
  • John P. Beilby2,14
  • Bu B. Yeap5,15
  • Oscar Millet16
  • Julien Wist1,17
  • Jeremy K. Nicholson18,19
  • Samantha Lodge1
  • Elaine Holmes19,20
20 affiliations
  1. 1Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth, WA Australia
  2. 2Busselton Population Medical Research Institute, Busselton, WA Australia
  3. 3Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA Australia
  4. 4School of Population and Global Health, University of Western Australia, Perth, WA Australia
  5. 5Medical School, University of Western Australia, Perth, WA Australia
  6. 6Perron Institute for Neurological and Translational Science, Nedlands, WA Australia
  7. 7Institute for Health Research, University of Notre Dame Australia, Fremantle, WA Australia
  8. 8School of Population Health, Curtin University, Perth, WA Australia
  9. 9Department of Cardiology and Internal Medicine, Royal Perth Hospital, Perth, WA Australia
  10. 10Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
  11. 11Drug Metabolism Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
  12. 12Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
  13. 13Bruker Biospin GmbH & Co. Kg, Ettlingen, Germany
  14. 14School of Biomedical Sciences, University of Western Australia, Perth, WA Australia
  15. 15Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA Australia
  16. 16Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain
  17. 17Chemistry Department, Universidad del Valle, Cali, Colombia
  18. 18Institute of Global Health Innovation, Imperial College London, London, UK
  19. 19School of Medicine, The Hong Kong University of Science and Technology, Hong Kong, China
  20. 20Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
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Abstract

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 1H 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.

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Cite

BibTeXRIS
BibTeX
@article{minaee2026high,
  title = {{High resolution lipoprotein subfraction profiling identifies obesity associated distributional changes in LDL and HDL subfractions and particle ratios}},
  author = {Novia Minaee and Reika Masuda and Philipp Nitschke and Drew Hall and Jennie Hui and Michael L. Hunter and Leon Flicker and Graeme J. Hankey and Osvaldo P. Almeida and Dick C. Chan and Gerald F. Watts and Muhammad Saeed Ahmad and Huda M. Alkreathy and Zoheir Abdullah Dhamanouri and Hartmut Schäfer and Manfred Spraul and Claire Cannet and John P. Beilby and Bu B. Yeap and Oscar Millet and Julien Wist and Jeremy K. Nicholson and Samantha Lodge and Elaine Holmes},
  journal = {International Journal of Obesity (2005)},
  year = {2026},
  month = aug,
  doi = {10.1038/s41366-026-02172-6},
  url = {https://doi.org/10.1038/s41366-026-02172-6},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - High resolution lipoprotein subfraction profiling identifies obesity associated distributional changes in LDL and HDL subfractions and particle ratios
AU  - Novia Minaee
AU  - Reika Masuda
AU  - Philipp Nitschke
AU  - Drew Hall
AU  - Jennie Hui
AU  - Michael L. Hunter
AU  - Leon Flicker
AU  - Graeme J. Hankey
AU  - Osvaldo P. Almeida
AU  - Dick C. Chan
AU  - Gerald F. Watts
AU  - Muhammad Saeed Ahmad
AU  - Huda M. Alkreathy
AU  - Zoheir Abdullah Dhamanouri
AU  - Hartmut Schäfer
AU  - Manfred Spraul
AU  - Claire Cannet
AU  - John P. Beilby
AU  - Bu B. Yeap
AU  - Oscar Millet
AU  - Julien Wist
AU  - Jeremy K. Nicholson
AU  - Samantha Lodge
AU  - Elaine Holmes
PY  - 2026
DA  - 2026/08/13
JO  - International Journal of Obesity (2005)
DO  - 10.1038/s41366-026-02172-6
UR  - https://doi.org/10.1038/s41366-026-02172-6
AB  - 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 1H 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.
SN  - 0307-0565
SN  - 1476-5497
ER  -