Key Molecules of Triglycerides Pathway Metabolism Are Disturbed in Patients With Systemic Lupus Erythematosus

Quevedo-Abeledo, Juan Carlos; Martín-González, Candelaria; Ferrer-Moure, Carmen; Armas-Rillo, Laura de; Hernández-Hernández, María; Ferraz‐Amaro, Iván

doi:10.3389/fimmu.2022.827355

Cited by 6 publications

(10 citation statements)

References 30 publications

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“…In this report, patients with RA showed higher serum levels of ANGPTL4 and ApoC‐III, but lower circulating LPL, compared with controls. Similar results have been described in systemic lupus erythematosus patients 13,14 …”

Section: Introductionsupporting

confidence: 86%

“…Both ANGPTL4 and ApoC‐III are endogenous modulators that inhibit LPL by modulating free fatty acid uptake in both fasting and fed states, 5 thereby interfering with the lipolysis of triglyceride‐rich lipoproteins 6 . In two previous studies by our group, the ANGPTL4, ApoC‐III, LPL and axis has been studied in RA and systemic lupus erythematosus patients 12,13 . In 323 patients with RA and 246 age‐matched controls, after multivariable analysis including cardiovascular risk factors, statin use and lipid profile changes caused by the disease itself, RA patients showed higher serum levels of ANGPTL4 and ApoC‐III, but lower circulating LPL 12 .…”

Section: Discussionmentioning

confidence: 99%

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Tocilizumab‐related hypertriglyceridemia is independent of key molecules regulating lipid metabolism

Ferraz‐Amaro

Santos-Concepción

Castro

et al. 2023

Eur J Clin Investigation

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IntroductionTocilizumab (TCZ) treatment is associated with dyslipidaemia, including a rise in triglycerides through a mechanism poorly understood. Three molecules play key roles in the regulation of triglyceride metabolism: apolipoprotein C‐III (ApoC‐III), angiopoietin‐like protein 4(ANGPLT4) and lipoprotein lipase (LPL). The aim of this work was to analyse whether the changes in triglycerides shown by TCZ‐treated RA patients could stem from the dysregulation that can occur in these regulatory molecules.MethodsTwenty‐seven RA patients included in the TOCRIVAR study who received TCZ (8 mg/kg IV/q4w) were evaluated at baseline and at Weeks 12, 24 and 52 of treatment. ANGPTL4, ApoC‐III and LPL, a complete lipid profile and RA disease activity, were analysed at baseline and at each visit. Multivariable linear mixed models were performed to study changes over time in lipids and regulatory molecules.ResultsAfter 24 weeks of TCZ treatment, HDL cholesterol, apolipoprotein A1 and triglycerides increased, whereas lipoprotein (a) decreased significantly from baseline values. However, 1 year after TCZ, no significant differences in lipid pattern were observed with respect to baseline. Serum ANGPTL4 and Apo‐CIII levels decreased gradually over time, both being significantly lower than baseline values at Week 52. LPL concentration did not change significantly during TCZ treatment. Remarkably, the elevation of triglycerides at Week 24 maintained its statistical significance after adjusting for the changes in ApoC‐III, ANGPTL4 and LPL.ConclusionIn TCZ‐treated RA patients basal serum levels of ANGPLT4 and ApoC‐III, but not LPL, decreased significantly. However, the elevation of triglycerides after TCZ was not related to changes in these regulatory molecules.

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Section: Introductionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Tocilizumab‐related hypertriglyceridemia is independent of key molecules regulating lipid metabolism

Ferraz‐Amaro

Santos-Concepción

Castro

et al. 2023

Eur J Clin Investigation

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“…This has been widely described in diseases such as systemic lupus erythematosus [ 14 , 15 ] and rheumatoid arthritis [ 16 ]. In addition, LPL is known to be upregulated in patients with systemic lupus erythematosus [ 17 ]. In this sense, the CRP and SLE disease damage index showed a positive and significant relationship with LPL.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease

Rodríguez-Hernández

Carrillo-Palau

Camba

et al. 2023

IJMS

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Disruption of the lipid profile is commonly found in patients with inflammatory bowel disease (IBD). Lipoprotein lipase (LPL) is a key molecule involved in triglyceride metabolism that plays a significant role in the progression of atherosclerosis. In this study, our aim was to study whether serum LPL levels are different in IBD patients and controls and whether IBD features are related to LPL. This was a cross-sectional study that encompassed 405 individuals; 197 IBD patients with a median disease duration of 12 years and 208 age- and sex-matched controls. LPL levels and a complete lipid profile were assessed in all individuals. A multivariable analysis was performed to determine whether LPL serum levels were altered in IBD and to study their relationship with IBD characteristics. After the fully multivariable analysis, including cardiovascular risk factors and the changes in lipid profile that the disease causes itself, patients with IBD showed significantly higher levels of circulating LPL (beta coefficient 196 (95% confidence interval from 113 to 259) ng/mL, p < 0.001). LPL serum levels did not differ between Crohn’s disease and ulcerative colitis. However, serum C-reactive protein levels, disease duration, and the presence of an ileocolonic Crohn’s disease phenotype were found to be significantly and independently positively related to LPL. In contrast, LPL was not associated with subclinical carotid atherosclerosis. In conclusion, serum LPL levels were independently upregulated in patients with IBD. Inflammatory markers, disease duration and disease phenotype were responsible for this upregulation.

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“…Beside LPL, the apolipoprotein C3–angiopoietin-like protein 4 axis is also disrupted in SLE, resulting in significantly lower ApoC3, and significantly higher ANGPLT4. Both of these are particularly important as regulators of triglyceride transport and are novel therapeutic targets [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus

Diószegi

Lőrincz

Kaáli³

et al. 2023

Biomolecules

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Background: Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association between dyslipidemia and early vascular damage. Patients and Methods: 51 clinically active SLE patients and 41 age- and gender-matched control subjects were enrolled in the study. Lipoprotein subfractions were detected by Lipoprint. Brachial artery flow-mediated dilation and common carotid intima-media thickness were detected by ultrasonography. Arterial stiffness indicated by augmentation index (Aix) and pulse wave velocity was measured by arteriography. Results: We found significantly higher Aix, higher VLDL ratio, plasma triglyceride, ApoB100, and small HDL, as well as lower HDL-C, large HDL, and ApoA1 in patients with SLE. There was a significant positive correlation of Aix with triglyceride, VLDL, IDL-C, IDL-B, and LDL1. A backward stepwise multiple regression analysis showed IDL-C subfraction to be the best predictor of Aix. Conclusions: Our results indicate that in young patients with SLE, triglyceride-rich lipoproteins influence vascular function detected by Aix. These parameters may be assessed and integrated into the management plan for screening cardiovascular risk in patients with SLE.

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Key Molecules of Triglycerides Pathway Metabolism Are Disturbed in Patients With Systemic Lupus Erythematosus

Cited by 6 publications

References 30 publications

Tocilizumab‐related hypertriglyceridemia is independent of key molecules regulating lipid metabolism

Tocilizumab‐related hypertriglyceridemia is independent of key molecules regulating lipid metabolism

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease

Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus

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