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Cited by 19Lipid metabolism and disordersAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

Lipidomics of triglyceride‐rich lipoproteins derived from hyperlipidemic patients on inflammation

Open access
Moreno‐Vedia, Juan, Llop, Dídac, Rodríguez‐Calvo, Ricardo, Plana, Núria, Amigó, Núria, Rosales, Roser, Esteban, Yaiza, Masana, Lluís +2 more·2024·European Journal of Clinical Investigation
DOI 10.1111/eci.14132
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Abstract

Background and aim: Triglyceride‐rich lipoproteins (TRLs) can have an important role in atherosclerosis development due to their size and ability to penetrate the endothelium. While high plasma triglyceride (TG) levels and chronic inflammation are relevant in metabolic diseases, it remains unclear whether TGs are atherogenic or which TRL‐TG‐derived metabolites are responsible for inflammation. Here, we aimed to study the lipidome modifications of TRL particles enriched in TG in patients with hyperlipidemia and their associations with a proinflammatory status both in vivo and in vitro. Methods: Using proton nuclear magnetic resonance (1 H‐NMR), we analysed the plasma levels of glycoprotein acetyls and the TRL lipidomic profile of 307 patients with dyslipidemia. THP‐1‐derived macrophages were used as an in vitro model to explore the molecular inflammatory effects mediated by TRL. Results: In vivo, higher TRL‐TG levels were associated with higher circulating levels of NMR‐measured glycoproteins (Glyc‐A, Glyc‐B and Glyc‐F; p < .001). Lipidomic analysis showed that TRL‐TG enrichment led to decreased cholesterol and phospholipid content (p < .01), an increase in omega‐9, and a decrease in saturated fatty acids (p < .001). THP‐1 macrophages exposed to increasing TRL particle concentrations augmented the secretion of IL‐1β and TNF‐α, which varied based on particle composition. Particles with higher cholesterol and phospholipid contents exerted higher cytokine secretion. The activation of MAPK, Akt/NFκB, and caspase‐1 was concurrent with this proinflammatory response. Conclusions: High TRL‐TG levels are associated with a higher systemic inflammatory status and increased particle concentrations. In vitro, higher particle numbers increase proinflammatory cytokine secretion, with cholesterol and phospholipid‐rich TRL being more proinflammatory.

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  • Systemically, TRLs and their remnants have been linked to markers of low-grade inflammation, including hs-CRP, circulating cytokines such as IL-6 and TNF-α, and immune cell activation.

    “Systemically, TRLs and their remnants have been linked to markers of low-grade inflammation, including hs-CRP, circulating cytokines such as IL-6 and TNF-α, and immune cell activation [22–28].”

    From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [27]

    The Discussion (section 4; page not supplied) links higher TRL levels with glycoprotein markers of low-grade systemic inflammation. It also says hs-CRP did not differ between groups. The paper reports TNF-α secretion and macrophage responses after TRL exposure in vitro, not circulating cytokine levels or systemic immune-cell activation; it does not establish the claimed IL-6 association. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Moreno‐Vedia, J., Llop, D., Rodríguez‐Calvo, R., Plana, N., Amigó, N., Rosales, R., Esteban, Y., Masana, L., Ibarretxe, D., & Girona, J.
Affiliations
  • Institut de Recerca Biomèdica Catalunya Sud (ES)
  • Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES)
Corresponding author
Ibarretxe, Daiana
ORCID
Venue
European Journal of Clinical Investigation
Publisher
Wiley
Published
2023-11-27
Volume
54
Issue
3
Pages
e14132-e14132
ISSN
  • 0014-2972 (ISSN-L)
  • 1365-2362
DOI
10.1111/eci.14132
OpenAlex
W4389069148
Cited by
19
References
4
Citations by year
2026: 6 · 2025: 10 · 2024: 3
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Clinical Investigation (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Rovira & Virgili repository (submittedVersion, cc-by)
Funders
Instituto de Salud Carlos III (PI18/00515)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
triglyceride-rich lipoproteins, hyperlipidemia, dyslipidemia, inflammation, lipidomics, glycoprotein acetyls, THP-1 macrophages, inflammatory cytokines, IL-1β, TNF-α, MAPK signaling, AKT/NF-κB signaling, caspase-1, atherosclerosis, omega-9 fatty acids, saturated fatty acids
MeSH terms
Lipidomics, Cholesterol, Humans, Hyperlipidemias, Inflammation, Lipoproteins, Phospholipids, Triglycerides, Cytokines

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