scholarly journals Lipoprotein distribution of Apo CIII glycoforms in healthy men is linked with low TG and increased insulin sensitivity

2020 ◽  
Author(s):  
Marina Rodríguez ◽  
Pere Rehues ◽  
Víctor Iranzo ◽  
Jorge Mora ◽  
Clara Balsells ◽  
...  

ABSTRACTGlycosylation of Apo CIII modulates its function in triglyceride metabolism, and some variants are associated with a protective or pro-atherogenic lipid profile. These associations have been studied in whole plasma Apo CIII proteoforms, but the proportion of Apo CIII proteoforms in individual lipoprotein fractions has been rarely evaluated. In the present study, we aim to measure the relative content of Apo CIII proteoforms in each lipoprotein fraction (VLDL, IDL, LDL and HDL) in a group of healthy subjects as a potential biomarker for triglyceride metabolism, cardiovascular risk and diabetes. Lipoprotein fractions were separated by differential ultracentrifugation of plasma samples. The relative concentrations of seven Apo CIII variants were measured by mass spectrometric immunoassay, and the complete lipoprotein profile was determined by NMR. The results showed high interindividual variability in the distribution of Apo CIII proteoforms across the study population but a uniform proportion in all lipoprotein fractions. Two Apo CIII variants, Apo CIII0b and Apo CIII1d, were negatively correlated with plasma and VLDL triglycerides regardless of VLDL size and were associated with increased LDL size when transported in LDL particles. Apo CIII0b also showed a negative correlation with lipoprotein-insulin resistance score. Therefore, Apo CIII variants can be reliably measured in lipoprotein fractions, and our results suggest that Apo CIII0b and Apo CIII1d have a protective role in triglyceride metabolism and insulin resistance in healthy individuals.

2019 ◽  
Vol 3 (8) ◽  
pp. 1503-1517 ◽  
Author(s):  
Alexandra B Kinzer ◽  
Robert D Shamburek ◽  
Marissa Lightbourne ◽  
Ranganath Muniyappa ◽  
Rebecca J Brown

Abstract Context Patients with lipodystrophy have dyslipidemia and insulin resistance. Leptin treatment with metreleptin in lipodystrophy decreases insulin resistance and lowers triglycerides without changing high-density lipoprotein. Detailed measurement of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into cardiovascular disease (CVD) risk and lipid metabolism beyond a standard lipid panel. We hypothesized that patients with lipodystrophy would have a more atherogenic lipid profile than controls at baseline, which would be ameliorated with metreleptin treatment. Objective To characterize the lipoprotein profile in patients with lipodystrophy compared with controls and to evaluate effects of metreleptin treatment. Design, Setting, Patients, and Intervention Patients with lipodystrophy (N = 17) were studied before and after metreleptin for 2 weeks and 6 months and compared with 51 insulin-sensitive sex-matched controls. Main Outcome Measures Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). Results Patients with lipodystrophy had elevated large TRLPs and smaller HDLPs and LDLPs compared with controls. Five patients with lipodystrophy had chylomicrons, compared with zero controls. Metreleptin decreased the size and concentration of TRLPs, eliminated chylomicrons in all but one patient, decreased LDLPs, and increased LDLP size. Metreleptin treatment did not have major effects on HDLPs. Conclusions Patients with lipodystrophy had an atherogenic lipoprotein profile at baseline consistent with elevated CVD risk, which improved after metreleptin treatment. The presence of fasting chylomicrons in a subset of patients with lipodystrophy suggests saturation of chylomicron clearance by lipoprotein lipase.


2019 ◽  
Vol 160 (3) ◽  
pp. 98-103 ◽  
Author(s):  
Márta Zsoldos ◽  
Attila Pajor ◽  
Henriette Pusztafalvi

Abstract: The prevalence of the metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, obesity and depression have increased during the recent years. As the sexual dysfunction is also frequent, we aimed to search for the associations between sexual dysfunction and the metabolic syndrome and its components, respectively, by reviewing the literature. The clinical and biochemical components of the metabolic syndrome included cardiovascular disease, type 2 diabetes mellitus, visceral obesity and depression, furthermore, insulin resistance, atherogenic lipid profile, hypogonadism, chronic systemic inflammation and endothelial dysfunction were all demonstrated to affect adversely the sexual function. The dysfunction of the sexual arousal response shows a strong association in men and a milder one in women with the cardiovascular diseases and depression. Sexual function in diabetes mellitus is mostly impaired by microvascular injury, polyneuropathy and autonomic neuropathy. Erectile dysfunction and disorder of the female sexual arousal response and the orgasm, respectively, are associated with insulin resistance, atherogenic lipid profile and systemic inflammatory condition in overweight or obese patients. Sexual dysfunction particularly in men can be an early sign of the severe complications of metabolic syndrome. The pathogenetic link between the metabolic syndrome and the sexual dysfunction seems to be the insulin resistance. Both metabolic syndrome and sexual dysfunction can be restored by altering the lifestyle. Orv Hetil. 2019; 160(3): 98–103.


Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5369-5376 ◽  
Author(s):  
Camilla Alexanderson ◽  
Elias Eriksson ◽  
Elisabet Stener-Victorin ◽  
Theodore Lystig ◽  
Britt Gabrielsson ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 47
Author(s):  
Pere Rehues ◽  
Marina Rodríguez ◽  
Judith Álvarez ◽  
Marta Jiménez ◽  
Alba Melià ◽  
...  

Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL (p < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors.


2005 ◽  
Vol 6 (1) ◽  
pp. 7
Author(s):  
P. Perez-Martinez ◽  
J. Lopez-Miranda ◽  
A. Lozano ◽  
J.A. Moreno ◽  
C. Bellido ◽  
...  

Epigenomics ◽  
2021 ◽  
Author(s):  
Aécio A Braga ◽  
Raul H Bortolin ◽  
Magda E Graciano-Saldarriaga ◽  
Thiago DC Hirata ◽  
Alvaro Cerda ◽  
...  

Aim: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Patients & methods: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). Results: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity C-reactive protein, IL-6, resistin and adiponectin (p < 0.05). Conclusion: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.


2020 ◽  
Author(s):  
Rana Halloun ◽  
Ahmad Ighbariya ◽  
Suhair Hanna ◽  
Ronit Sinnreich ◽  
Ram Weiss

Abstract Background: Palestinians exhibit a substantially greater prevalence of type 2 diabetes mellitus, cardiovascular disease (CVD) incidence and CVD mortality in comparison to Israelis. In view of Palestinians' increased insulin resistance, known to be associated with an adverse lipoprotein profile, we aimed at showing lipoprotein variations between Palestinian and Israelis residing in Jerusalem. Methods: The study included, 968 Palestinians and 707 Israelis, ages 25-74 years, who underwent fasting and 2h post oral challenge plasma glucose determinations. We evaluated metabolic risk by measuring sub-populations of VLDL, LDL and HDL particles, using nuclear magnetic resonance spectroscopic analysis. Results: Palestinians exhibit higher levels of very large VLDL including chylomicrons, in comparison to their Israeli counterparts, whereas levels of medium and small VLDL were similar between the two populations. Small oxidized LDL levels were higher among Palestinians while intermediate and large LDL were similar between the two groups. Levels of large HDL were higher among Israelis while levels of medium and small HDL were similar between the two populations. Small oxidized LDL levels were higher among Palestinians in comparison to Israeli participants. Levels of large HDL were higher among Israelis in comparison to Palestinians. Limiting the analysis to young participants with normal glucose tolerance, showed greater levels of large VLDL including chylomicrons, medium and small VLDL and oxidized LDL in Palestinians. Conclusions: Palestinians, including healthy young participants, exhibit an adverse pro-atherogenic lipid profile compared to Israelis. These findings may explain the increased CVD morbidity and mortality observed in Palestinians.


2016 ◽  
Vol 62 (5) ◽  
pp. 45-46
Author(s):  
Paulina Ormazabal ◽  
Beatrice Scazzocchio ◽  
Rosaria Varì ◽  
Annunziata Iacovelli ◽  
Roberta Masella

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB. Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.


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