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. 2025 Jan 8;24(1):9.
doi: 10.1186/s12933-024-02553-z.

Triglyceride-independent associations between circulating levels of apolipoprotein C-III and biomarkers of inflammation

Dídac Llop  1   2   3 , Pere Rehues  1   2   3 , Silvia Paredes  1   2   4 , Montse Guardiola  1   2   3 , Josefa Girona  1   2   3 , Roser Rosales  1   2   3 , Yaiza Esteban  1   2   3 , Lluís Masana  1   2   3   5 , Daiana Ibarretxe  1   2   3   5 , Joan-Carles Vallvé  6   7   8   9 , Josep Ribalta  1   2   3
Affiliations

Triglyceride-independent associations between circulating levels of apolipoprotein C-III and biomarkers of inflammation

Dídac Llop et al. Cardiovasc Diabetol. .

Abstract

Backgrounds and aims: Preclinical studies suggest that a triglyceride (TG)-independent proinflammatory action of apolipoprotein C-III (apoCIII) exists. We aimed to investigate the relationship between circulating apoCIII levels and subclinical inflammation markers across different cohorts with distinctive inflammatory patterns: patients with metabolic disorders (MDs), patients with rheumatoid arthritis (RA), and controls. Specifically, we assessed the associations of apoCIII with acute inflammation biomarkers (e.g., high sensitivity C-reactive protein (hsCRP)) and novel systemic inflammation biomarkers (e.g., glycosylated proteins: Glyc-A, Glyc-B, Glyc-F), aiming to understand the role of apoCIII beyond its traditional function in TG metabolism.

Methods: This cross-sectional study involved 1242 participants: 906 patients with MD (metabolic syndrome, type 2 diabetes (T2DM) and/or obesity), 192 patients with RA, and 144 controls. ApoCIII and hsCRP levels were measured via immunoturbidimetric assays, and glycosylated proteins were quantified via 1 H-NMR spectroscopy. Correlation and multivariate linear regression analyses were conducted.

Results: ApoCIII levels were significantly and positively associated with Glyc-A, Glyc-B, and Glyc-F levels across all cohorts. Most of these associations remained significant in the MD group after adjusting for TG levels. Conversely, negative associations were detected between apoCIII and hsCRP patients with MD and RA, which were maintained after including TG in the models.

Conclusion: In patients with MD and RA, circulating apoCIII levels were positively associated with glycoproteins and negatively with hsCRP, in a TG-independent manner. Our results suggest that apoCIII is associated with the low-grade inflammatory profile represented by glycoproteins, independent of triglyceride levels. Additionally, we observed a negative association with hsCRP, which, while seemingly paradoxical, has been reported in previous studies.

Keywords: Apolipoprotein-CIII; C-reactive protein; Glycoproteins; Inflammation; Metabolic disorders.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Spearman correlations of ApoCIII levels with CRP, Glyc-A, Glyc-B and Glyc-F levels in the three different cohorts. A = apoCIII–CRP, B = apoCIII–Glyc-A, C = apoCIII–Glyc-B, D = apoCIII–Glyc-F RA = rheumatoid arthritis; MD = metabolic disorder; CRP = high-sensitivity C–reactive protein; Glyc-A = glycoprotein A; Glyc-B = glycoprotein B; Glyc-F = glycoprotein F
Fig. 2
Fig. 2
Multivariate linear regressions evaluating the associations of ApoCIII levels with CRP, Glyc-A, Glyc-B and Glyc-F levels in patients with MD, patients with RA and healthy control participants. P-value is adjusted by the Benjamini & Hochberg method RA = rheumatoid arthritis; MD = metabolic disorder; CRP = C-reactive protein; Glyc-A = glycoprotein A; Glyc-B = glycoprotein B; Glyc-F = glycoprotein F; CI = confidence interval
Fig. 3
Fig. 3
Multivariate linear regressions evaluating the associations of ApoCIII levels with CRP, Glyc-A, Glyc-B and Glyc-F levels in patients the subgroup of patients with T2DM. P-value is adjusted by the Benjamini & Hochberg method CRP = C-reactive protein; Glyc-A = glycoprotein A; Glyc-B = glycoprotein B; Glyc-F = glycoprotein F
Fig. 4
Fig. 4
Multivariate linear regressions evaluating the associations of ApoCIII levels with CRP, Glyc-A, Glyc-B and Glyc-F levels in patients the subgroup of patients with hypertriglyceridemia. P-value is adjusted by the Benjamini & Hochberg method CRP = C-reactive protein; Glyc-A = glycoprotein A; Glyc-B = glycoprotein B; Glyc-F = glycoprotein F
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