María del Mar Roca-Rodríguez

Effect of acute and chronic red wine consumption on lipopolysaccharide concentrations

BACKGROUND Chronic red wine (RW) consumption has been associated with decreased cardiovascular disease risk, mainly attributed to an improvement in lipid profile. RW intake is also able to change the composition of gut microbiota. High fat intake has recently been reported to increase metabolic endotoxemia. The gut microbiota has been proposed as the main resource of plasma lipopolysaccharides (LPSs) in metabolic endotoxemia. OBJECTIVE We analyzed the effect on LPS concentrations of chronic RW consumption and acute RW intake in relation to high fat intake in middle-aged men. DESIGN For the chronic study, 10 middle-aged male volunteers were randomly assigned in a crossover trial, and after a washout period, all subjects received RW, dealcoholized red wine (DRW), or gin for 20 d. Serum endotoxin and LPS-binding protein (LBP) concentrations were determined after the washout period and after each of the treatments, and changes in fecal microbiota were quantified. For the acute study, 5 adult men underwent a fat overload or a fat overload together with the consumption of RW, DRW, or gin. Baseline and postprandial serum LPS and LBP concentrations and postprandial chylomicron LPS concentrations were measured. RESULTS There were no significant differences in the change in LPS or LBP concentrations between chronic RW, DRW, and gin consumption. Bifidobacterium and Prevotella amounts were significantly increased by RW and correlated negatively with LPS concentrations. There were no differences in postprandial serum LPS, LBP, or chylomicron LPS concentrations between acute RW, DRW, or gin intake together with a fatty meal. CONCLUSION Chronic RW consumption increases Bifidobacterium and Prevotella amounts, which may have beneficial effects by leading to lower LPS concentrations. This trial was registered at controlled-trials.com as ISRCTN88720134.

Effects of glucagon‐like peptide‐1 on the differentiation and metabolism of human adipocytes

Glucagon‐like peptide‐1 (GLP‐1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP‐1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up‐regulated in AT of insulin‐resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP‐1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects.

Effects of GLP‐1 on the differentiation and metabolism of human adipocytes

Glucagon‐like peptide‐1 (GLP‐1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP‐1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up‐regulated in AT of insulin‐resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP‐1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects.

Parathyroid hormone-related protein, human adipose-derived stem cells adipogenic capacity and healthy obesity

OBJECTIVE This study aimed to define the potential role of PTHrP on adipogenic regulation and to analyze its relationship with obesity and insulin resistance. DESIGN This was a cross-sectional study in which visceral (VAT) and subcutaneous (SAT) adipose tissue were extracted from 19 morbidly obese, 10 obese, and 10 lean subjects. PTHrP mRNA levels were measured in VAT and SAT. VAT mesenchymal stem cells and 3T3-L1 cells were differentiated into adipocytes in presence or absence of PTHrP siRNA. PTHrP mRNA and protein levels as well as adipogenic markers were evaluated by Western blotting or qPCR. Immunohistochemistry and immunofluorescence procedures were used for PTHrP intracellular localization. RESULTS Both human VAT and SAT express PTHrP protein mainly in the nucleolar compartment of stromal vascular fraction cells. The highest levels of PTHrP mRNA and protein expression were detected in undifferentiated mesenchymal cells and progressively decreased during adipogenesis. Remarkably, adipogenic differentiation in human mesenchymal stem cells (A-hMSC) was significantly impaired in a pthrp knockdown. PTHrP seems to be related to obesity-associated insulin resistance (IR), given that we found that PTHrP mRNA expression was higher in VAT from morbidly obese with a low IR degree (MO-L-IR) subjects than those from morbidly obese with a high IR degree (MO-H-IR) and lean subjects, and correlated positively with body mass index and hip circumference. We also found that A-hMSC from MO-L-IRs displayed higher adipogenic capacity than those from both MO-H-IRs and leans. In addition, adipogenesis was impaired in VAT from MO-H-IRs, given that mRNA expression levels of key adipogenic regulators were lower than those from MO-L-IR subjects. CONCLUSIONS PTHrP could be a potential new therapeutic target for the reprograming of adipogenesis and adipose tissue expansion, thus possibly ameliorating the metabolic syndrome in obese subjects.

CCNG2 and CDK4 is associated with insulin resistance in adipose tissue

BACKGROUND The involvement of cyclin G2 (CCNG2) and cyclin-dependent kinase-4 (CDK4), cell cycle regulatory proteins, in adipose tissue metabolism and insulin resistance is still unknown. The objective of this study was to analyze CCNG2 and CDK4 levels in visceral (VAT) and subcutaneous adipose tissue (SAT) from nonobese and morbidly obese patients and their relationship with insulin resistance. METHODS We studied the mRNA and protein levels of CCNG2 and CDK4 in VAT and SAT from 12 nonobese and 23 morbidly obese patients (11 with low [MO-L-IR] and 12 with high insulin resistance [MO-H-IR]). RESULTS The nonobese patients had a significantly greater CCNG2 expression in VAT (P = .004) and SAT (P<.001) than the MO-L-IR and MO-H-IR patients. The MO-H-IR patients had a significantly lower CDK4 expression in VAT than the MO-L-IR (P = .026), but similar to the nonobese patients. CDK4 and CCNG2 expression correlated significantly in VAT (r = 0.511, P<.001) and SAT (r = .535, P = .001). In different multiple regression analysis models, CCNG2 and CDK4 expression in VAT was mainly predicted by glucose (P = .047 and P = .008, respectively), and CCNG2 expression in SAT was mainly predicted by body mass index (P = .041). No significant associations were found with CDK4 expression in SAT. Moreover, VAT CCNG2 expression was the main determinant of the improvement in the homeostasis model assessment of insulin resistance index at 3 months after bariatric surgery (B = -271.7, P = .026). CONCLUSION Our data show for the first time that the human CCNG2 and CDK4 expression of VAT are inversely associated with glucose and insulin resistance.

Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus

espanolAntecedentes La diabetes mellitus gestacional es un factor de riesgo importante para el sindrome metabolico y la enfermedad cardiovascular. Objetivos Se evaluaron las relaciones entre los componentes del sindrome metabolico, los niveles de citocinas y moleculas de adhesion en mujeres con diabetes gestacional durante el embarazo y en el posparto. Pacientes y metodos Estudio prospectivo de casos y controles. Se analizaron 126 mujeres gestantes (63 con diabetes mellitus gestacional y 63 controles). En el periodo posparto, se reevaluaron 41 casos y 21 controles. Se analizaron variables clinicas, niveles de citocinas y moleculas de adhesion durante las semanas 24-29 de la gestacion y 12 meses despues del parto. Resultados En el periodo posparto, el factor de necrosis tumoral alfa en casos y controles, y la adiponectina en controles fueron significativamente mas altos. Los casos mostraron mayores niveles de leptina, sin diferencias significativas durante el embarazo y despues del parto. No se observaron diferencias significativas en las moleculas de adhesion y la interleucina 6 entre casos y controles durante el periodo de embarazo y el posparto, pero ambos fueron mayores en los casos. Durante el embarazo y posparto, la adiponectina disminuyo en los casos y aumento en los controles. Observamos correlaciones positivas significativas entre adiponectina con glucemia en ayunas y moleculas de adhesion celular vascular-1, y entre leptina y factor de necrosis tumoral alfa. Conclusiones Los resultados indican que el aumento de la inflamacion y la hiperglucemia transitoria durante el embarazo representarian una forma latente de sindrome metabolico, con un mayor riesgo de diabetes mellitus tipo 2 y de enfermedad cardiovascular en el futuro. EnglishBackground Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease. Aims To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery. Patients and methods A prospective case–control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24–29 of pregnancy and 12 months after delivery. Results In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels. Conclusions The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease.

Effects of exercise on inflammation in cardiac rehabilitation

BACKGROUND Programs of weight loss and a healthy diet are recommended for patients with cardiovascular risk but the effectiveness of these programs in decreasing cardiovascular mortality is controversial. AIM To examine the acute and long-term effects of a 2-month cardiac rehabilitation program on chemokines related to inflammation in subjects with cardiovascular disease. DESIGN Prospective cohort study. METHODS Twenty-six patients with cardiovascular disease enrolled in a cardiac rehabilitation program based on nutritional and exercise interventions were studied. Lifestyle and clinical, metabolic and inflammatory variables were analysed. RESULTS 88.5% were men and the mean age was 54.9 ± 7.8 years. At the end of the cardiac rehabilitation program the levels of carbohydrate and lipid metabolism were lower, except for high density lipoprotein cholesterol which was higher. The levels of uric acid, interleukin-6, interleukin-1Beta, adiponectin and leptin remained stable. Interleukin-6 correlated positively with levels of C-reactive protein and negatively with blood glucose. Interleukin-1Beta correlated positively with C-reactive protein levels and negatively with blood pressure figures. Significant correlations were seen between the changes in levels of interleukin-6 and interleukin-1Beta and changes in metabolic equivalents, and in C-reactive protein levels before and after the cardiac rehabilitation program. No significant correlations were observed with weight, waist circumference or fat mass. CONCLUSIONS A cardiac rehabilitation program decreased anthropometric variables and blood pressure figures, and improved lipid metabolism and ergometry data. However, no changes regarding the inflammatory state were observed.

Long-term effects of varying consumption of ω3 fatty acids in ear, nose and throat cancer patients: assessment 1 year after radiotherapy

Abstract A prospective 1-year follow-up study in ear, nose, and throat (ENT) cancer patients was carried out one year after radiotherapy to assess the effect of varying consumption of ω3 fatty acid according to whether they consumed more or less than the 50th percentile of ω3 fatty acids. Clinical, analytical, inflammatory (CRP and IL-6), and oxidative variables (TAC, GPx, GST, and SOD) were evaluated. The study comprised 31 patients (87.1% men), with a mean age of 61.3 ± 9.1 years. Hematological variables showed significant differences in the patients with a lower consumption of ω3 fatty acids. A lower mortality and longer survival were found in the group with ω3 fatty acid consumption ≥50th percentile but the differences were not significant. No significant difference was reached in toxicity, inflammation, and oxidative stress markers. The group with ω3 fatty acid consumption <50th percentile significantly experienced more hematological and immune changes.