RESUMO
Altered organokine expression contributes to increased cardiometabolic risk in obesity. Our aim was to evaluate the associations of serum afamin with glucose homeostasis, atherogenic dyslipidemia, and other adipokines in severe obesity to clarify the early metabolic alterations. 106 non-diabetic obese (NDO) subjects and 62 obese patients with type 2 diabetes matched for age, gender, and body mass index (BMI) were enrolled in this study. We compared their data with 49 healthy, lean controls. Serum afamin and retinol-binding protein 4 (RBP4), as well as plasma plasminogen activator inhibitor-1 (PAI-1), were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Afamin and PAI-1 found to be significantly higher in the NDO and T2M group (p < 0.001 and p < 0.001, respectively) than in the controls. In contrast, RBP4 was unexpectedly lower in the NDO and T2DM group compared to controls (p < 0.001). Afamin showed negative correlations with mean LDL size and RBP4, but positive correlations with anthropometric, glucose/lipid parameters, and PAI-1 in both the overall patients and the in NDO + T2DM groups. BMI, glucose, intermediate HDL, and small HDL were predictors of afamin. Afamin may serve as a biomarker for the severity of cardiometabolic disturbances in obesity. The complexity of organokine patterns in NDO subjects draws attention to the diverse spectrum of obesity-related comorbidities.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Índice de Massa Corporal , Glucose , Proteínas Plasmáticas de Ligação ao RetinolRESUMO
Cholesteryl ester transfer protein (CETP) is known to influence HDL-C levels, potentially altering the profile of HDL subfractions and consequently cardiovascular risk (CVR). This study aimed to investigate the effect of five single-nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene on 10-year CVR estimated by the Systematic Coronary Risk Evaluation (SCORE), the Framingham Risk Score for Coronary Heart Disease (FRSCHD) and Cardiovascular Disease (FRSCVD) algorithms. Adjusted linear and logistic regression analyses were used to investigate the association of SNPs and 10 haplotypes (H1-H10) on 368 samples from the Hungarian general and Roma populations. The T allele of rs7499892 showed a significant association with increased CVR estimated by FRS. H5, H7, and H8 showed a significant association with increased CVR based on at least one of the algorithms. The impact of H5 was due to its effect on TG and HDL-C levels, while H7 showed a significant association with FRSCHD and H8 with FRSCVD mediated by a mechanism affecting neither TG nor HDL-C levels. Our results suggest that polymorphisms in the CETP gene may have a significant effect on CVR and that this is not mediated exclusively by their effect on TG and HDL-C levels but also by presently unknown mechanisms.
Assuntos
Doenças Cardiovasculares , Proteínas de Transferência de Ésteres de Colesterol , Humanos , Proteínas de Transferência de Ésteres de Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Haplótipos , Doenças Cardiovasculares/genética , Fatores de Risco , HDL-Colesterol/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco de Doenças CardíacasRESUMO
Type 2 diabetes mellitus (T2DM) is a major global public health problem, as it is associated with increased morbidity, mortality, and healthcare costs. Insulin resistance (IR) is a condition characterized by disturbances in carbohydrate and lipid metabolism that precedes T2DM. The aim of the present study was to investigate the association between HDL and its subfraction profile and the progression of IR, as assessed by the Homeostatic Model Assessment for IR (HOMA-IR) index, and to define cut-off values to identify an increased risk of IR. Individuals with a HOMA-IR greater than 3.63 were considered to have IR. The HDL subfractions were separated using the Lipoprint system, which identifies ten subfractions (HDL-1-10) in three subclasses as large (HDL-L), intermediate (HDL-I) and small (HDL-S). Analyses were performed on samples from 240 individuals without IR and 137 with IR from the Hungarian general and Roma populations. The HDL-1 to -6 subfractions and the HDL-L and -I classes showed a significant negative association with the progression and existence of IR. Among them, HDL-2 (B = -40.37, p = 2.08 × 10-11) and HDL-L (B = -14.85, p = 9.52 × 10-10) showed the strongest correlation. The optimal threshold was found to be 0.264 mmol/L for HDL-L and 0.102 mmol/L and above for HDL-2. Individuals with HDL-L levels below the reference value had a 5.1-fold higher risk of IR (p = 2.2 × 10-7), while those with HDL-2 levels had a 4.2-fold higher risk (p = 3.0 × 10-6). This study demonstrates that the HDL subfraction profile (especially the decrease in HDL-2 and -L) may be a useful marker for the early detection and intervention of atherogenic dyslipidemia in subjects with impaired glucose and insulin metabolism.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Lipoproteínas HDL2 , Glucose , Custos de Cuidados de SaúdeRESUMO
Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration.
Assuntos
Diabetes Mellitus Tipo 2 , Hormônios Peptídicos , Masculino , Feminino , Humanos , Proteína 8 Semelhante a Angiopoietina , Diabetes Mellitus Tipo 2/complicações , Lipoproteínas , Lipoproteínas LDL , Obesidade/complicações , Lipoproteínas VLDLRESUMO
Background: Diabetic neuropathy (DN) is a very frequent microvascular complication of type 2 diabetes mellitus (T2DM). Obesity and physical inactivity are well-known risk factors for T2DM. Fibroblast growth factor 21 (FGF21) is a liver-secreted hormone with several beneficial effects on obesity-related metabolic disorders. We aimed to investigate the effect of short-term physical activity on the levels of FGF21, and its correlation with the severity of peripheral sensory polyneuropathy in T2DM patients. Methods: Thirty patients with DN were enrolled in the study, compared to age- and gender-matched controls. We conducted a six-week aerobic training program, which meant treadmill and cycle ergometers three times a week. Anthropometric and laboratory parameters were measured for each patient before and after intervention. Serum levels of FGF21, TNF-alpha, irisin, leptin and adiponectin were measured by ELISA. The sensory perception threshold (CPT) was quantitatively measured using Neurometer®. Results: We found significant decreases in BMI, waist circumference, HbA1c and TNF-alpha levels. From baseline to six-week follow-up, FGF21 levels were significantly increased in DN patients. Significant negative correlations were shown between the changes in FGF21 levels and BMI, between changes in FGF21 and the improvement of CPT values, and between the changes in FGF21 and TNF-alpha levels. There was no difference in irisin, adiponectin and leptin levels in DN patients after aerobic training program. Conclusions: The physical activity may increase the level of FGF21 in T2DM patients with neuropathy. Our results highlight the importance of regular physical activity in the treatment of diabetic neuropathy.
RESUMO
BACKGROUND: Pigment epithelium-derived factor (PEDF) is a serin protease inhibitor and a potent inhibitor of angiogenesis. Its serum level has significant associations with metabolic parameters. However, little is known about the association between PEDF levels and lipid parameters in renal transplanted (TX) patients. Therefore, our aim was to investigate the relationship between PEDF level and lipid parameters in TX patients. METHODS: Seventy TX patients (47 males, 23 females, mean age 51.7 ± 12.4 years) and 34 healthy controls were enrolled. We examined the serum creatinine, C-reactive protein, fasting glucose and lipid parameters right before, then 1 and 6 months after TX. High-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. PEDF and oxidized low-density liporotein (oxLDL) levels were measured by ELISA. RESULTS: Before transplantation, patients had had a significantly higher PEDF level compared to control subjects (p < 0.001). One month after transplantation, their PEDF level decreased significantly reaching the healthy controls' level, and this lower level was maintained during the 6 months follow-up period as well. The initial oxLDL level was significantly higher, while PON1 activities were significantly lower in the patient group compared to the control group. We found a significant positive correlation between PEDF and total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, oxLDL and small HDL subfraction; while negative correlations were found between PEDF and mean LDL size and large HDL subfraction during the entire follow-up period. CONCLUSION: PEDF may play an important role in the increased oxidative stress and enhanced atherogenesis in renal transplant patients.
Assuntos
Falência Renal Crônica , Transplante de Rim , Serpinas , Adulto , Arildialquilfosfatase , Proteína C-Reativa , Colesterol , Creatinina , Proteínas do Olho , Feminino , Glucose , Humanos , Falência Renal Crônica/cirurgia , Lipoproteínas , Lipoproteínas HDL , Lipoproteínas LDL , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural , TriglicerídeosRESUMO
STUDY OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep-related breathing disorder, characterized by excessive daytime sleepiness (EDS), paralleled by intermittent collapse of the upper airway. EDS may be the symptom of OSAHS per se but may also be due to the alteration of central circadian regulation. Irisin is a putative myokine and has been shown to induce BDNF expression in several sites of the brain. BDNF is a key factor regulating photic entrainment and consequent circadian alignment and adaptation to the environment. Therefore, we hypothesized that EDS accompanying OSAHS is reflected by alteration of irisin/BDNF axis. METHODS: Case history, routine laboratory parameters, serum irisin and BDNF levels, polysomnographic measures and Epworth Sleepiness Scale questionnaire (ESS) were performed in a cohort of OSAHS patients (n = 69). Simple and then multiple linear regression was used to evaluate data. RESULTS: We found that EDS reflected by the ESS is associated with higher serum irisin and BDNF levels; ß: 1.53; CI: 0.35, 6.15; p = 0.012 and ß: 0.014; CI: 0.0.005, 0.023; p = 0.02, respectively. Furthermore, influence of irisin and BDNF was significant even if the model accounted for their interaction (p = 0.006 for the terms serum irisin, serum BDNF and their interaction). Furthermore, a concentration-dependent effect of both serum irisin and BDNF was evidenced with respect to their influence on the ESS. CONCLUSIONS: These results suggest that the irisin-BDNF axis influences subjective daytime sleepiness in OSAS patients reflected by the ESS. These results further imply the possible disruption of the circadian regulation in OSAHS. Future interventional studies are needed to confirm this observation.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Fibronectinas/sangue , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Sonolência , Adulto , Idoso , Biomarcadores , Ritmo Circadiano/fisiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Apneia Obstrutiva do Sono/epidemiologiaRESUMO
BACKGROUND: Obestatin is a ghrelin-associated peptide, derived from preproghrelin. Although many of its effects are unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. To date, level of obestatin and its correlations to the lipid subfractions in non-diabetic obese (NDO) patients have not been investigated. METHODS: Fifty NDO patients (BMI: 41.96 ± 8.6 kg/m2) and thirty-two normal-weight, age- and gender-matched healthy controls (BMI: 24.16 ± 3.3 kg/m2) were enrolled into our study. Obestatin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions, intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) levels and mean LDL size were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint). RESULTS: Serum level of obestatin was significantly lower in NDO patients compared to controls (3.01 ± 0.5 vs. 3.29 ± 0.6 µg/ml, p < 0.05). We found significant negative correlations between the level of obestatin and BMI (r = - 0.33; p < 0.001), level of serum glucose (r = - 0.27, p < 0.05), HbA1c (r = - 0.38; p < 0.001) and insulin (r = - 0.34; p < 0.05). Significant positive correlation was found between obestatin level and the levels of ApoA1 (r = 0.25; p < 0.05), large HDL subfraction ratio and level (r = 0.23; p < 0.05 and r = 0.24; p < 0.05), IDL (r = 0.25 p < 0.05) and mean LDL size (r = 0.25; p < 0.05). Serum VLDL ratio and level negatively correlated with obestatin (r = - 0.32; p < 0.01 and r = - 0.21; p = 0.05). In multiple regression analysis obestatin was predicted only by VLDL level. CONCLUSIONS: Based on our data, measurement of obestatin level in obesity may contribute to understand the interplay between gastrointestinal hormone secretion and metabolic alterations in obesity.
Assuntos
Grelina/sangue , Lipoproteínas/sangue , Obesidade/sangue , Adulto , Arildialquilfosfatase/sangue , Estudos de Casos e Controles , Diabetes Mellitus/sangue , Feminino , Humanos , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Masculino , Pessoa de Meia-Idade , Peroxidase/sangueRESUMO
BACKGROUND: Afamin is a plasma vitamin E-binding glycoprotein partially associated with ApoA1-containing high-density lipoprotein (HDL) subfractions. In a previous study, the serum vitamin E decreased after low-density lipoprotein (LDL) apheresis, while vitamin E/cholesterol ratio increased. We aimed to study the effect of LDL apheresis on serum afamin level. METHODS: The serum level of afamin and oxidized LDL were measured by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments and in seven healthy controls. We also investigated the changes in total cholesterol, LDL-C, HDL-C, ApoB, ApoA1, HDL subfractions, and α- and γ-tocopherol levels during the treatment. HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Serum α- and γ-tocopherol levels were detected by gas chromatography-mass spectrometry. RESULTS: The first treatment sessions decreased serum afamin levels by an average of 9.4%. Total cholesterol, LDL-C, HDL-C and ApoA1 levels decreased by 52.6; 61.8; 10.5; and 14.1%, respectively. We found that α- and γ-tocopherol levels markedly decreased (by 34.1 and 32.9%, respectively), while α- tocopherol/cholesterol and γ-tocopherol/cholesterol ratios significantly increased (by 41.4 and 40.3%, respectively). Oxidized LDL levels significantly decreased. There was a shift toward the larger HDL subfractions. CONCLUSION: LDL apheresis moderately decreases the circulating levels of afamin parallel to lowering HDL-C and ApoA1 levels. Tocopherol levels decreases markedly compared to afamin levels, however, beneficial changes in vitamin E/cholesterol ratios, oxidized LDL levels and HDL subfraction distribution were detected. These additional effects of LDL apheresis may result in further cardiovascular risk reduction in FH patients.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Proteínas de Transporte/sangue , Glicoproteínas/sangue , Lipoproteínas LDL/isolamento & purificação , Vitamina E/sangue , Apolipoproteína A-I/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , HDL-Colesterol/sangue , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Lipoproteínas LDL/sangue , Albumina Sérica Humana , Tocoferóis/sangueRESUMO
BACKGROUND: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. PATIENTS AND METHODS: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. RESULTS: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. CONCLUSIONS: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.
Assuntos
Arildialquilfosfatase/sangue , Hiperlipidemias/sangue , Sobrepeso/sangue , Peroxidase/sangue , Adulto , Idoso , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Ligante de CD40/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/enzimologia , Molécula 1 de Adesão Intercelular/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/diagnóstico , Sobrepeso/enzimologia , Valor Preditivo dos Testes , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
BACKGROUND: Selective low-density lipoprotein (LDL) apheresis is commonly used to treat patients with familial hypercholesterolemia (FH). Chemerin is an adipokine with putative roles in the regulation of lipid metabolism. METHODS: In our pilot study, we measured serum chemerin levels by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments using the technique of direct adsorption of lipoproteins (DALI). RESULTS: The first treatment sessions decreased serum chemerin levels by an average of 27.26 %. While following one patient, 12 months of regular LDL apheresis resulted in a permanent reduction in his serum chemerin level. Changes in the lipoprotein subfractions measured by gel electrophoresis (Lipoprint) correlated with the reduction of chemerin levels. Furthermore, we eluted and then measured chemerin bound to the DALI column. CONCLUSION: We conclude that LDL apheresis decreases the circulating level of chemerin by binding the protein to the column and thus improves lipoprotein subfraction pattern.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Quimiocinas/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Lipoproteínas LDL/administração & dosagem , Adsorção , Idoso , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/patologia , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients. METHODS: Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined. RESULTS: HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 ± 26.87 vs. 148.35 ± 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 ± 58.28% vs. 217.71 ± 54.36%, p < 0.001) were significantly reduced in patients compared to controls. Additionally, all HDL subfraction concentrations were significantly decreased in patients, while the levels of the examined inflammatory markers were significantly elevated in SLE subjects. The latter correlated positively with disease activity, and negatively with HDL concentration and total HDL antioxidant capacity, respectively. PON1 arylesterase activity and erythrocyte sedimentation rate were independent predictors of total HDL antioxidant capacity. CONCLUSIONS: Induced by the systemic inflammation, altered composition and antioxidant activity may diminish the anti-atherogenic effect of HDL and therefore may contribute to the increased cardiovascular risk of SLE patients.
Assuntos
Antioxidantes/metabolismo , Arildialquilfosfatase/sangue , Lipoproteínas HDL/sangue , Lúpus Eritematoso Sistêmico/metabolismo , Adulto , Apolipoproteína A-I/sangue , Arildialquilfosfatase/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , HDL-Colesterol/sangue , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Interleucina-6/sangue , Lipoproteínas HDL/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Masculino , Estresse OxidativoRESUMO
BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a rare disease caused by biallelic mutation in the 7-dehydrocholesterol (7DHC) reductase gene. High oxidizability of 7DHC and the appearance of small-sized low-density lipoprotein (LDL) subfractions indicate increased endogenous oxidative stress that is counterbalanced by natural antioxidant defense mechanisms including the high-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme. PON1 prevents lipoproteins from oxidative modifications; however, PON1 activity and the distribution of lipoprotein subfractions have not been studied in SLOS. METHODS: 7DHC levels and PON1 arylesterase activities were measured spectrophotometrically in 11 SLOS patients and 10 healthy children. Lipoprotein subfractions were detected by polyacrylamide gel electrophoresis. RESULTS: Compared to controls, there was a shift towards the small-dense LDL subfraction and the large HDL subfraction in SLOS. PON1 arylesterase activity was significantly decreased in SLOS patients and correlated negatively with the proportion of small-dense LDL subfraction and the proportion of large HDL subfraction. Significant positive correlations were detected between PON1 arylesterase activity and the ratios of intermediate and small HDL subfractions. CONCLUSIONS: Decreased PON1 activity and the deleterious shift in the distribution of lipoprotein subfractions may contribute to the impaired antioxidant status observed in SLOS. Monitoring of serum PON1 arylesterase activity may be a complementary biomarker in SLOS.
Assuntos
Antioxidantes/metabolismo , Lipoproteínas HDL/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/sangue , Síndrome de Smith-Lemli-Opitz/sangue , Arildialquilfosfatase/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , HDL-Colesterol/sangue , Feminino , Humanos , Lipídeos/sangue , Masculino , Estresse Oxidativo , Oxigênio/químicaRESUMO
The prevalence of obesity has been increasing worldwide. Chemerin is a recently discovered adipokine secreted by the enlarged adipose tissue with diverse biological effects that are not well detailed yet. This study aimed to elucidate the potential role of chemerin in oxidative stress and inflammation that are characteristics for excess weight and may eventually lead to insulin resistance and atherosclerotic complications. We also analysed the associations between chemerin and classical adipokines, namely leptin and adiponectin. Therefore, we investigated non-diabetic obese patients without manifest cardiovascular disease and compared their data to healthy lean individuals. Chemerin correlated positively with markers of oxidative stress and inflammation, while it showed a negative correlation with the measure of antioxidant status, characterized by the HDL-linked paraoxonase-1 enzyme. Chemerin also correlated positively with leptin and negatively with adiponectin respectively. In our study population, oxidized low-density lipoprotein and high-sensitivity C-reactive protein were found to be the strongest predictors of chemerin level. We conclude that chemerin may contribute to chronic inflammation and increased oxidative stress in obese individuals, even in the absence of manifest insulin resistance.
Assuntos
Adipocinas/metabolismo , Biomarcadores/metabolismo , Proteínas Quimerinas/metabolismo , Inflamação/patologia , Obesidade/patologia , Estresse Oxidativo , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Arildialquilfosfatase/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Inflamação/complicações , Resistência à Insulina , Leptina/metabolismo , Lipoproteínas LDL/metabolismo , Obesidade/etiologiaRESUMO
OBJECTIVE: Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared with lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear. PATIENTS AND METHODS: Fifty nondiabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint). RESULTS: We detected significantly higher serum chemerin levels in NDO patients compared with healthy controls (590·1 ± 190·3 ng/ml vs 405 ± 127·1 ng/ml, P < 0·001). A significant positive correlation was found between chemerin and LDL cholesterol levels, while chemerin showed a significant negative correlation with the level of HDL cholesterol. Significant positive correlation was detected between chemerin and the ratio of small dense LDL, while chemerin correlated negatively with the mean LDL size. Also, a significant negative correlation was found between serum chemerin and the ratio of large HDL subfraction, while there were significant positive correlations between chemerin levels and intermediate and small HDL subfraction ratios, respectively. CONCLUSION: Chemerin may be involved in the regulation of lipoprotein metabolism in obese patients who do not show apparent abnormalities of glucose metabolism. Early changes in the distribution of the lipoprotein subfractions may contribute to the progression of atherosclerosis, leading to increased cardiovascular risk.
Assuntos
Quimiocinas/sangue , Lipoproteínas/sangue , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangueRESUMO
Obesity and its co-morbidities as metabolic syndrome, type 2 diabetes mellitus and cardiovascular diseases are major health problems worldwide. Several reports indicated that nutrient excess and metabolic syndrome are linked with altered immune response. Indeed, metabolic syndrome is characterized by insulin resistance and chronic low-grade inflammation, which conditions are the consequences of the complex interaction between adipocytes and immune cells. Enlarged white adipose tissue is infiltrated by immune cells and secretes various bioactive substances, like adipokines, cytokines and other inflammatory mediators. Due to its special architecture in which metabolic and immune cells are in intimate proximity, metabolic and immunologic pathways are closely integrated in adipose tissue. With the contribution of altered gut microbiota, adipokines and cytokines modulate insulin signaling and immune response leading to adipose tissue inflammation and systemic insulin resistance. In this chapter, we focus on the cellular and molecular mechanisms that lead to impaired insulin sensitivity and chronic low-grade inflammation in obesity. We also detail the potential role of adipokines and immune cells in this deleterious process, and the concerns of vaccination in metabolic syndrome. Finally, we address the links between obesity and gut microbiota as an emerging new field of interest, and scratch the surface of potential therapeutic opportunities.
Assuntos
Adipocinas/imunologia , Doenças Cardiovasculares/imunologia , Mediadores da Inflamação/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Síndrome Metabólica/imunologia , Animais , Doenças Cardiovasculares/patologia , Citocinas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Intestinos/patologia , Síndrome Metabólica/patologiaRESUMO
Cerebrotendinous xanthomatosis is a rare neurodegenerative disease characterized by the accumulation of cholesterol and cholestanol in the brain and the tendons caused by mutations of the gene encoding sterol 27-hydroxylase (CYP27A1), which is involved in bile acid synthesis. The diagnosis is often missed and delayed because of the variable clinical presentation of the disease. Blood testing for cerebrotendinous xanthomatosis is routinely performed using gas chromatography-mass spectrometry measurement of elevated cholestanol level, and the diagnosis is confirmed by molecular genetic analysis. Early recognition and initiation of chenodeoxycholic acid therapy with hydoxymethylglutarylCoenzyme-A reductase inhibitors is critical to prevent irreversible neurological damage and permanent disability. The authors summarize the current knowledge about the pathomechanism, laboratory diagnosis and therapeutic options of cerebrotendinous xanthomatosis.
Assuntos
Ácido Quenodesoxicólico/uso terapêutico , Colestanotriol 26-Mono-Oxigenase/genética , Colestanol/metabolismo , Colesterol/metabolismo , Xantomatose Cerebrotendinosa/diagnóstico , Xantomatose Cerebrotendinosa/metabolismo , Encéfalo/metabolismo , Colestanol/sangue , Colesterol/sangue , Técnicas de Laboratório Clínico , Diagnóstico Precoce , Cromatografia Gasosa-Espectrometria de Massas , Regulação Enzimológica da Expressão Gênica , Testes Genéticos/economia , Saúde Global , Humanos , Hungria/epidemiologia , Recém-Nascido , Triagem Neonatal , Doenças Raras , Tendões/metabolismo , Xantomatose Cerebrotendinosa/tratamento farmacológico , Xantomatose Cerebrotendinosa/enzimologia , Xantomatose Cerebrotendinosa/genética , Xantomatose Cerebrotendinosa/fisiopatologiaRESUMO
Selenium is an essential trace element with potential anti-atherogenic and antioxidant effects. Experimental data suggest that selenium might be beneficial in the prevention of atherosclerosis and its complications, whereas human epidemiological studies have yielded conflicting results. Data on hair selenium status in hyperlipidemic patients are still lacking. Therefore, we analysed selenium concentrations by X-ray fluorescence in the hair of 81 statin-naïve patients with newly diagnosed Fredrickson-type IIa and IIb hyperlipoproteinemia and compared their data with 43 healthy volunteers. We also assessed the frequency of other classical risk factors of atherosclerosis. Hair selenium levels were found to be significantly higher in hyperlipidemic patients compared with volunteers with normal lipid levels. Also, a significantly increased number of traditional atherosclerosis risk factors were observed in hyperlipidemic patients with hair selenium concentrations above the median in contrast to those with below. Our results suggest that high hair selenium status might be associated with adverse blood lipid profile together with an increased number of traditional risk factors in a selenium-deplete population. These findings warrant further investigations to study the impact of selenium supplementation on the incidence of cardiovascular events.
Assuntos
Aterosclerose/diagnóstico , Biomarcadores/análise , Cabelo/química , Hiperlipidemias/metabolismo , Selênio/análise , Aterosclerose/etiologia , Aterosclerose/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Hiperlipidemias/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Selênio/metabolismo , Espectrometria por Raios XRESUMO
OBJECTIVE: The aim of this study was to clarify the effect of Apolipoprotein E (ApoE) polymorphism on the efficacy of cholesterol absorption inhibitor ezetimibe monotherapy on lipid parameters. METHODS: 63 hyperlipidemic patients with statin induced adverse effects were involved in the study. We examined the effect of 10 mg/day ezetimibe treatment on lipid levels after 3, 6 and 12 months of treatment in patients on a diet of only different ApoE genotypes. RESULTS: Three months of ezetimibe treatment significantly decreased the total cholesterol (TC) (-10.1%), low-density lipoprotein (LDL-C) (-12.0%) (p < 0.001) and triglyceride (Tg) (-8%) levels (p < 0.05). After 6 and 12 months of treatment reduction in TC, LDL-C and Tg levels were even more pronounced. The genotype distribution of the patients were 2/2: 4.8%, 2/3: 7.9%, 3/3: 68.3%, 3/4: 19.0%. There were no patients with 2/4 and 4/4 genotypes. In patients with 2/3, 3/3 or 3/4 genotype, the ezetimibe treatment tended to be more effective on TC and LDL-C levels than in the 2/2 group, and the efficacy of ezetimibe on Tg levels were slightly better in 2/2 carriers compared to other patients. CONCLUSIONS: The ApoE genotype does not predict the efficacy of ezetimibe treatment on serum lipid parameters.
Assuntos
Anticolesterolemiantes/uso terapêutico , Apolipoproteínas E/genética , Azetidinas/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Idoso , Colesterol/sangue , LDL-Colesterol/sangue , Ezetimiba , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
We aimed to investigate serum amino-terminal C-type natriuretic peptide (NT-proCNP) and its relationship with quantitative and qualitative HDL-parameters in patients with end-stage renal disease (ESRD) before, then 1 and 6 months after kidney transplantation (TX). Seventy patients (47 males, 23 females, mean age 51.7 ± 12.4 years) were enrolled in a prospective follow-up study. We examined serum creatinine, C-reactive protein, procalcitonin, fasting glucose and lipid parameters before, then 1 and 6 months after TX. High-density lipoprotein- (HDL)-associated paraoxonase-1 (PON1) paraoxonase and arylesterase activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. NT-proCNP and oxidized low-density lipoprotein (oxLDL) levels were measured by ELISA. Mean NT-proCNP was 45.8 ± 21.9 pmol/L before renal transplantation and decreased markedly 1 month and 6 months after transplantation (5.3 ± 2.5 and 7.7 ± 4.9 pmol/L, respectively, P = 1 × 10-4). During the 6 months' follow-up, PON1 arylesterase, paraoxonase and salt-stimulated paraoxonase activities improved. NT-proCNP positively correlated with procalcitonin and creatinine and negatively with GFR, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C). There was a negative correlation between serum NT-proCNP and PON1 arylesterase activity. According to the multiple regression analysis, the best predicting variables of NT-proCNP were serum procalcitonin, creatinine and PON1 arylesterase activity. NT-proCNP might be a novel link between HDL dysfunction and impaired vascular function in ESRD, but not after kidney transplantation. Further studies in larger populations are needed to clarify the exact role of NT-proCNP in the risk prediction for cardiovascular comorbidities and complications in ESRD.