Joan Vendrell

Publications (79)377.77 Total impact

• Article: Gender determines the actions of adiponectin multimers on fetal growth and adiposity.

  Inmaculada Simón-Muela, Silvia Näf, Mónica Ballesteros, Joan Vendrell, Victoria Ceperuelo-Mallafre, Miriam de la Flor, Ana Megia
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  ABSTRACT: OBJECTIVE: To analyze the role of cord blood adiponectin and its multimeric forms in neonatal adiposity and fetal growth (FGV) during the third trimester of pregnancy according to fetal gender. STUDY DESIGN: Prospective analytical observational study conducted at the Diabetes and Pregnancy unit, University Hospital Joan XXIII, Tarragona. Ninety-six healthy pregnant women were included in the early third trimester and were followed up until delivery. Maternal blood was obtained upon recruitment, and cord blood was obtained at delivery. Serial fetal ultrasounds were performed during the third trimester to assess fetal growth velocity. Skinfolds were measured after birth to assess neonatal adiposity. Adiponectin multimers were determined in maternal and cord blood. RESULTS: In female neonates, adiposity and fetal growth velocity in the late third trimester were correlated positively with cord blood insulin (cbinsulin) (r:0.343; p=0.015 and r:0.430;p=0.002, respectively) and maternal pregravid BMI (r:597;p<0.001 and r:0.428;p=0.002, respectively), and negatively with maternal High Molecular Weight (HMW)/total adiponectin ratio (r:-0.269;p=0.035 and r:-0.387;p=0.005, respectively), but in the stepwise multiple regression model, the main determinants were cbinsulin, pregravid BMI and cord blood HMW adiponectin. Otherwise, in male neonates, adiposity and fetal growth were correlated with cord blood low molecular weight adiponectin (LMW) (r:0.486;p=0.003 and r:0.394;p=0.020, respectively), and it was this multimeric form that emerged as an independent determinant in the stepwise regression model. CONCLUSION: Adiponectin seems to determine fetal growth and adipose tissue accretion, and LMW is more specifically implicated in males, whereas the HMW isoform may be more important in females.
  American journal of obstetrics and gynecology 03/2013; · 3.28 Impact Factor
• Article: Circulating levels of lipocalin-2 and retinol-binding protein-4 are increased in psoriatic patients and correlated with baseline PASI.

  Jorge Romaní, Assumpta Caixàs, Victoria Ceperuelo-Mallafré, José Manuel Carrascosa, Miquel Ribera, Mercedes Rigla, Joan Vendrell, Jesús Luelmo
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  ABSTRACT: Psoriasis has been related to metabolic syndrome (MS). Adipocytokines produced by white adipose tissue may be involved in the pathogenesis of psoriasis and its association with MS. Our objectives were to characterize the profile of a number of different inflammatory and atherogenic markers, vitamins, adipokines and cytokines and their potential involvement in MS in patients with moderate-to-severe psoriasis without joint involvement compared to anthropometrically matched controls, and to evaluate correlation with severity of the skin disease and changes after narrow-band UVB (NB-UVB) phototherapy. We designed a prospective cross-sectional study. Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine and vitamins D, B6, B12 and folic acid, leptin, resistin, omentin, lipocalin-2, adipocyte fatty acid-binding protein, retinol-binding protein-4 (RBP-4), interleukin-6, soluble tumour necrosis factor receptor 1 (sTNFR1) and interleukin-17 of 50 psoriasis patients and 50 gender, age and body mass index-matched controls were recorded, then evaluated after NB-UVB in the patients. The patients had higher baseline serum concentrations of leptin, RBP-4, lipocalin-2 and sTNFR1. Baseline psoriasis area and severity index correlated with serum concentrations of RBP-4 and lipocalin-2 only. Principal components analysis disclosed a component including vitamins B12, B6, folic acid, calcidiol and HDL-cholesterol that was only present in healthy controls and opposed to a cluster of variables which promote MS. This component was absent in the patients. Our results point to lipocalin-2 and RBP-4 as relevant mediators of the trend towards MS in psoriatic patients.
  Archives for Dermatological Research 12/2012; · 2.28 Impact Factor
• Article: Ethinyl Estradiol-Cyproterone Acetate Versus Low-Dose Pioglitazone-Flutamide-Metformin for Adolescent Girls with Androgen Excess: Divergent Effects on CD163, TWEAK Receptor, ANGPTL4, and LEPTIN Expression in Subcutaneous Adipose Tissue.

  Marta Díaz, Matilde R Chacón, Abel López-Bermejo, Elsa Maymó-Masip, Cristina Salvador, Joan Vendrell, Francis de Zegher, Lourdes Ibáñez
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  ABSTRACT: Objective: The aim was to compare the effects of a traditional therapy (an oral estroprogestagen) to those of a novel treatment (a low-dose combination of generics) in adolescent girls with androgen excess. Study Design and Methods: In an open-label trial over 1 yr, 34 adolescents (age, 16 yr; body mass index, 23 kg/m(2)) with hyperinsulinemic androgen excess and without pregnancy risk were randomized to receive daily ethinyl estradiol-cyproterone acetate (EE-CA; Diane 35 Diario) or a low-dose combination of pioglitazone 7.5 mg/d, flutamide 62.5 mg/d, and metformin 850 mg/d (PioFluMet). Markers of androgen excess, C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and gene expression in longitudinal biopsies of sc adipose tissue at the abdominal level (RT-PCR) were assessed at baseline and after 1 yr. Results: EE-CA and low-dose PioFluMet reduced androgen excess comparably, but had divergent effects on C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, lean mass, abdominal and visceral fat, and on the expression of CD163, leptin, TNF-like weak inducer of apoptosis receptor, and angiopoietin-like protein 4, respectively, related to macrophage activation, fat accretion, inflammation, and lipoprotein metabolism in adipose tissue. All these divergences pointed to a healthier condition on low-dose PioFluMet. Conclusion: EE-CA and PioFluMet are similarly effective in reversing androgen excess over 1 yr, but low-dose PioFluMet is superior in reversing inflammatory, metabolic, and cardiovascular anomalies that are often associated with androgen excess.
  The Journal of clinical endocrinology and metabolism 07/2012; 97(10):3630-8. · 6.50 Impact Factor
• Article: A nontargeted proteomic approach to the study of visceral and subcutaneous adipose tissue in human obesity.

  María Insenser, Rafael Montes-Nieto, Nuria Vilarrasa, Albert Lecube, Rafael Simó, Joan Vendrell, Héctor F Escobar-Morreale
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  ABSTRACT: Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in biochemical and metabolic properties, especially when obesity is present. We submitted paired SAT and VAT samples from six morbidly obese patients and six non-obese persons to two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometry. Compared with non-obese subjects, obese patients presented with increased carboxylesterase-1, zinc finger protein 324A, annexin A5, ubiquitin carboxyl-terminal hydrolase, α-crystallin B chain, osteoglycin, retinal dehydrogenase-1 and 14-3-3 protein γ, and decreased transferrin, complement C3, fibrinogen γ chain, albumin, α1-antitrypsin and peroxiredoxin-6, irrespective of the adipose tissue depot studied. SAT and VAT differed in protein species of fibrinogen and osteoglycin, whereas adipose tissue depot and obesity interacted on the protein abundance of actin, α-actinin 1, one protein species of carboxylesterase-1, retinal dehydrogenase-1 and 14-3-3 protein γ. Our nontargeted proteomic approach identified novel protein species that may be involved in the development of obesity in humans.
  Molecular and Cellular Endocrinology 07/2012; 363(1-2):10-9. · 4.19 Impact Factor
• Article: TNF-α inhibits PPARβ/δ activity and SIRT1 expression through NF-κB in human adipocytes.

  Lucía Serrano-Marco, Matilde R Chacón, Elsa Maymó-Masip, Emma Barroso, Laia Salvadó, Martin Wabitsch, Lourdes Garrido-Sánchez, Francisco J Tinahones, Xavier Palomer, Joan Vendrell, Manuel Vázquez-Carrera
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  ABSTRACT: The mechanisms linking low-grade chronic inflammation with obesity-induced insulin resistance have only been partially elucidated. PPARβ/δ and SIRT1 might play a role in this association. In visceral adipose tissue (VAT) from obese insulin-resistant patients we observed enhanced p65 nuclear translocation and elevated expression of the pro-inflammatory cytokines TNF-α and IL-6 compared to control subjects. Inflammation was accompanied by a reduction in the levels of SIRT1 protein and an increase in PPARβ/δ mRNA levels. Stimulation of human mature SGBS adipocytes with TNF-α caused similar changes in PPARβ/δ and SIRT1 to those reported in obese patients. Unexpectedly, PPAR DNA-binding activity and the expression of PPARβ/δ-target genes was reduced following TNF-α stimulation, suggesting that the activity of this transcription factor was inhibited by cytokine treatment. Interestingly, the PPARβ/δ ligand GW501516 prevented the expression of inflammatory markers and the reduction in the expression of PPARβ/δ-target genes in adipocytes stimulated with TNF-α. Consistent with a role for NF-κB in the changes caused by TNF-α, treatment with the NF-κB inhibitor parthenolide restored PPAR DNA-binding activity, the expression of PPARβ/δ-target genes and the expression of SIRT1 and PPARβ/δ. These findings suggest that the reduction in PPARβ/δ activity and SIRT1 expression caused by TNF-α stimulation through NF-κB helps perpetuate the inflammatory process in human adipocytes.
  Biochimica et Biophysica Acta 06/2012; 1821(9):1177-85. · 4.66 Impact Factor
• Article: Plasma brain-derived neurotrophic factor in prepubertal obese children: results from a 2-year lifestyle intervention programme.

  Raquel Corripio, José-Miguel Gónzalez-Clemente, Pérez-Sánchez Jacobo, Näf Silvia, Gallart Lluis, Vendrell Joan, Caixàs Assumpta
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  ABSTRACT: Brain-derived neurotrophic factor (BDNF) is a neurotrophin potentially involved in the pathophysiology of obesity and metabolic syndrome in adults. In children, it has scarcely been studied. To analyse plasma BDNF and its relationship with metabolic syndrome components before and after 2 years of a lifestyle intervention programme in a prepubertal obese cohort. Case-control study with a 2-year prospective follow-up in a referral paediatric endocrine outpatient centre. Seventy-three prepubertal obese children, 8·03 ± 1·08 years old, and 47 age- and gender-matched lean controls were studied. Anthropometric parameters, blood pressure, platelet count (PLT), oral glucose tolerance test, homoeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, BDNF, diet and physical activity were evaluated. Weight loss was considered if z-score body mass index (BMI) decreased at least 0·5 SD. At baseline, BDNF tended to be lower in prepubertal obese children compared with lean controls (P = 0·076). BDNF did not correlate with any metabolic syndrome component. After 2 years, obese patients showed an increase in BDNF. Regression model analysis adjusted by age, sex, puberty, BMI, PLT and HOMA-IR showed that BDNF increased in subjects who lost weight (P = 0·036), practiced sports (P = 0·008) and had an adequate carbohydrate intake (P = 0·032). Plasma BDNF tends to be lower in obese prepubertal children than in lean controls, is not related to any other metabolic syndrome component and increases after a lifestyle intervention programme.
  Clinical Endocrinology 05/2012; 77(5):715-20. · 3.17 Impact Factor
• Article: Resveratrol induces antioxidant defence via transcription factor Yap1p.

  Xavier Escoté, Merce Miranda, Sandra Menoyo, Boris Rodríguez-Porrata, Didac Carmona-Gutiérrez, Helmut Jungwirth, Frank Madeo, Ricardo R Cordero, Albert Mas, Francisco Tinahones, Josep Clotet, Joan Vendrell
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  ABSTRACT: Resveratrol is a polyphenol suggested to play a protective role against ageing and age-related diseases. We demonstrate that administering low-doses of resveratrol causes ROS accumulation and transcriptional changes in yeast cells and human adipocytes. These changes in gene expression depend on the oxidative transcription factor Yap1p. In particular, resveratrol induces expression of Yap1p gene targets, such as TRX2, TRR1 or AHP1, in a Yap1p-dependent mode. Under resveratrol treatment, Yap1p is phosphorylated and accumulated in the nucleus. Yap1p knockout causes resveratrol sensitivity, which totally depends on the presence of the C-terminal region of Yap1p. Thus, resveratrol may enhance cellular lifespan by hormetic ROS accumulation, which leads to strengthening the cells' antioxidant capacity.
  Yeast 04/2012; 29(7):251-63. · 1.89 Impact Factor
• Article: Regulation of Bone Mineral Density in Morbidly Obese Women: A Cross-sectional Study in Two Cohorts Before and After Bypass Surgery

  José Manuel Gómez, Núria Vilarrasa, Carles Masdevall, Jordi Pujol, Esther Solano, Juan Soler, Iñaki Elio, Lluis Gallart, Joan Vendrell
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  ABSTRACT: BackgroundThe mechanisms by which increased body weight influence bone mass density (BMD) are still unknown. The aim of our study was to analyze the relationship between anthropometric and body composition variables, insulin growth factor-I (IGF-I), adiponectin and soluble tumor necrosis factor-α receptors (sTNFR) 1 and 2 with BMD in two cohorts of morbid obese patients, before and after bypass surgery. MethodsThe first cohort included 25 women aged 48 ± 7.6years studied before bypass surgery. The second included 41 women aged 46 ± 9.2years, 12months after surgery. We studied anthropometric variables obtained from whole body DEXA composition analysis. Serum IGF-I, intact serum parathyroid hormone, 25-hydroxivitamin D3, plasma adiponectin concentrations, sTNFR1, sTNFR2 concentrations were measured. ResultsIn the first cohort, the BMI was 44.5 ± 3.6kg/m2, parathyroid hormone, IGF-I, and adiponectin concentrations were lower, and sTNFR1 concentrations were higher than in the second cohort. In the multiple regression analysis, BMD remained significantly associated with body fat percentage (β −0.154, p = 0.01), lean mass (β 0.057, p = 0.016) and phosphate concentration (β 0.225, p = 0.05). In the second cohort, BMI was 31 ± 5.1kg/m2. In the multiple regression analysis, BMD remained significantly associated with lean mass (β 0.006, p = 0.03). ConclusionThe inverse correlation found between body fat and BMD in the first cohort indicates morbid obesity increases the risk of osteoporosis and we found a positive correlation with lean and fat mass before bariatric surgery and with lean mass after bypass surgery.
  Obesity Surgery 04/2012; 19(3):345-350. · 3.29 Impact Factor
• Article: Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy.

  Sergi Veloso, Xavier Escoté, Victòria Ceperuelo-Mallafré, Miguel López-Dupla, Joaquim Peraire, Consuelo Viladés, Pere Domingo, Antoni Castro, Montserrat Olona, Joan-Josep Sirvent, Manuel Leal, Joan Vendrell, Cristóbal Richart, Francesc Vidal
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  ABSTRACT: Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin, adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected patients treated with antiretroviral drugs (132 with lipodystrophy and 150 without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R, ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with or without lipodystrophy (p<0.001 for both comparisons) and were lower in patients with lipodystrophy compared with those without lipodystrophy (p=0.006). In patients with lipodystrophy, leptin had a positive correlation with insulin and with HOMA-IR. Adiponectin levels were non-significantly different in UC and HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels than non-lipodystrophy subjects (p<0.001). In patients with lipodystrophy, adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides. Plasma IL18 levels were higher in HIV-1-infected patients compared with UC (p<0.001), and no differences were found according to the presence of lipodystrophy. In patients with lipodystrophy there was a negative correlation between IL18 levels and LDLc. Genetic analyses indicated no significant associations with lipodystrophy nor with insulin resistance or with lipid abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin levels. This reduction is magnified in patients with lipodystrophy whose adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma IL18 levels are increased in infected patients irrespective of the presence of lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy or metabolic disturbances in treated HIV-1-infected patients.
  Cytokine 02/2012; 58(2):253-60. · 3.02 Impact Factor
• Article: FABP4 Dynamics in Obesity: Discrepancies in Adipose Tissue and Liver Expression Regarding Circulating Plasma Levels.

  María Isabel Queipo-Ortuño, Xavier Escoté, Victoria Ceperuelo-Mallafré, Lourdes Garrido-Sanchez, Merce Miranda, Mercedes Clemente-Postigo, Rafael Pérez-Pérez, Belen Peral, Fernando Cardona, Jose Manuel Fernández-Real, Francisco J Tinahones, Joan Vendrell
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  ABSTRACT: FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.
  PLoS ONE 01/2012; 7(11):e48605. · 4.09 Impact Factor
• Article: Zinc-α2-Glycoprotein Is Unrelated to Gestational Diabetes: Anthropometric and Metabolic Determinants in Pregnant Women and Their Offspring.

  Silvia Näf, Xavier Escote, Rosa Elena Yañez, Mónica Ballesteros, Inmaculada Simón, Pilar Gil, Ana Megia, Joan Vendrell
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  ABSTRACT: Zinc-α2-Glycoprotein (ZAG) is an adipokine with lipolytic action and is positively associated with adiponectin in adipose tissue. We hypothesize that ZAG may be related with hydrocarbonate metabolism disturbances observed in gestational diabetes mellitus (GDM). The aim of this study was to analyze serum ZAG concentration and its relationship with carbohydrate metabolism in pregnant women and its influence on fetal growth. 207 pregnant women (130 with normal glucose tolerance (NGT) and 77 with GDM) recruited in the early third trimester and their offspring were studied. Cord blood was obtained at delivery and neonatal anthropometry was assessed in the first 48 hours. ZAG was determined in maternal serum and cord blood. ZAG concentration was lower in cord blood than in maternal serum, but similar concentration was observed in NGT and GDM pregnant women. Also similar levels were found between offspring of NGT and GDM women. In the bivariate analysis, maternal ZAG (mZAG) was positively correlated with adiponectin and HDL cholesterol, and negatively correlated with insulin and triglyceride concentrations, and HOMA index. On the other hand, cord blood ZAG (cbZAG) was positively correlated with fat-free mass, birth weight and gestational age at delivery. After adjusting for confounding variables, gestational age at delivery and HDL cholesterol emerged as the sole determinants of cord blood ZAG and maternal ZAG concentrations, respectively. mZAG was not associated with glucose metabolism during pregnancy. ZAG concentration was lower in cord blood compared with maternal serum. cbZAG was independently correlated with gestational age at delivery, suggesting a role during the accelerated fetal growth during latter pregnancy.
  PLoS ONE 01/2012; 7(12):e47601. · 4.09 Impact Factor
• Source

  Available from: Xavier Escoté

  Article: Zinc-alpha 2-glycoprotein gene expression in adipose tissue is related with insulin resistance and lipolytic genes in morbidly obese patients.

  Lourdes Garrido-Sánchez, Eduardo García-Fuentes, Diego Fernández-García, Xavier Escoté, Juan Alcaide, Pablo Perez-Martinez, Joan Vendrell, Francisco J Tinahones
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  ABSTRACT: Zinc-α(2) glycoprotein (ZAG) stimulates lipid loss by adipocytes and may be involved in the regulation of adipose tissue metabolism. However, to date no studies have been made in the most extreme of obesity. The aims of this study are to analyze ZAG expression levels in adipose tissue from morbidly obese patients, and their relationship with lipogenic and lipolytic genes and with insulin resistance (IR). mRNA expression levels of PPARγ, IRS-1, IRS-2, lipogenic and lipolytic genes and ZAG were quantified in visceral (VAT) and subcutaneous adipose tissue (SAT) of 25 nondiabetic morbidly obese patients, 11 with low IR and 14 with high IR. Plasma ZAG was also analyzed. The morbidly obese patients with low IR had a higher VAT ZAG expression as compared with the patients with high IR (p = 0.023). In the patients with low IR, the VAT ZAG expression was greater than that in SAT (p = 0.009). ZAG expression correlated between SAT and VAT (r = 0.709, p<0.001). VAT ZAG expression was mainly predicted by insulin, HOMA-IR, plasma adiponectin and expression of adiponectin and ACSS2. SAT ZAG expression was only predicted by expression of ATGL. ZAG could be involved in modulating lipid metabolism in adipose tissue and is associated with insulin resistance. These findings suggest that ZAG may be a useful target in obesity and related disorders, such as diabetes.
  PLoS ONE 01/2012; 7(3):e33264. · 4.09 Impact Factor
• Source

  Available from: Eduardo García-Fuentes

  Article: De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery.

  Lourdes Garrido-Sánchez, Joan Vendrell, Diego Fernández-García, Victoria Ceperuelo-Mallafré, Matilde R Chacón, Luis Ocaña-Wilhelmi, Juan Alcaide, Francisco J Tinahones, Eduardo García-Fuentes
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  ABSTRACT: De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes. We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression ≥ P50 before bariatric surgery had a lower percentage hip circumference loss (<P50) after bariatric surgery (SAT: P = 0.039; VAT: P = 0.033). A lower basal ACSS2, ACC1 and ACL expression, genes involved in de novo lipogenesis, is associated with a better evolution of anthropometric variables after bariatric surgery. Thus, the previous state of the pathways involved in fatty acid metabolism may have repercussions on the improvement of these patients.
  PLoS ONE 01/2012; 7(2):e31280. · 4.09 Impact Factor
• Article: Structural damage in diabetic nephropathy is associated with TNF-α system activity.

  José Manuel Fernández-Real, Joan Vendrell, Isabel García, Wifredo Ricart, Martí Vallès
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  ABSTRACT: In experimental animal studies, tumour necrosis factor-α (TNF-α) contributed to renal hypertrophy during diabetes, and antibodies against TNF-α have led to improved histological lesions in animals with nephrotoxicity and diabetic nephropathy. We aimed to evaluate TNF-α system activity in association with renal histology in patients with type 2 diabetes. This is a prospective, cross-sectional study of 22 patients with type 2 diabetes (16 men), 13 with microalbuminuria and 9 with normoalbuminuria. Plasma-soluble TNF-α receptor 1 and 2 (sTNFR1 and sTNFR2) concentrations were used as surrogates of TNF-α system activity. Glomerular filtration rate (GFR) was analysed using I(125)-Iodothalamine. Albumin excretion rate (AER) and a renal biopsy were performed in all subjects. AER did not associate significantly with mesangial expansion or interstitial fraction in these subjects (r < 0.12, P > 0.5). AER was also not associated with either sTNFR1 or sTNFR2 levels. However, after controlling for GFR, the correlation between AER and sTNFR1 became significant (r = 0.47, P = 0.03). sTNFR1 correlated with age (r = 0.65, P < 0.001), mesangial expansion (r = 0.59, P = 0.004) and interstitial fraction (r = 0.58, P = 0.005). After controlling for age, body mass index and blood pressure, the association of TNFR1 with mesangial expansion persisted significant. Circulating sTNFR2 concentrations were not significantly associated with histological changes. In summary, structural kidney damage in patients with type 2 diabetes is associated with TNF-α system activity and specifically with plasma sTNFR1 concentrations.
  Acta Diabetologica 11/2011; 49(4):301-5. · 2.78 Impact Factor
• Article: Maternal and cord blood adiponectin multimeric forms in gestational diabetes mellitus: a prospective analysis.

  Mónica Ballesteros, Inmaculada Simón, Joan Vendrell, Victoria Ceperuelo-Mallafré, Ramon M Miralles, Gerard Albaiges, Francisco Tinahones, Ana Megia
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  ABSTRACT: To analyze the relationship between maternal adiponectin (mAdiponectin) and cord blood adiponectin (cbAdiponectin) multimeric forms (high molecular weight [HMW], medium molecular weight [MMW], and low molecular weight [LMW]) in a cohort of gestational diabetes mellitus (GDM) and normal glucose-tolerant (NGT) pregnant women. A total of 212 women with a singleton pregnancy, 132 with NGT and 80 with GDM, and their offspring were studied. Maternal blood was obtained in the early third trimester and cord blood was obtained at delivery. Total adiponectin and the multimeric forms of adiponectin were determined in cord blood and maternal serum. Spearman rank correlation and stepwise linear correlation analysis were used to assess the relationship between cbAdiponectin levels and clinical and analytical parameters. No differences in cbAdiponectin concentration or its multimeric forms were observed in the offspring of diabetic mothers compared with NGT mothers. The HMW-to-total adiponectin ratio was higher in cord blood than in maternal serum, whereas the MMW- and LMW-to-total adiponectin ratio was lower. Cord blood total and HMW adiponectin levels were positively correlated with birth weight and the ponderal index (PI), whereas cord blood MMW adiponectin was negatively correlated with the PI. In addition, cbAdiponectin and its multimeric forms were correlated with mAdiponectin concentrations. In the multivariate analysis, maternal multimeric forms of adiponectin emerged as independent predictors of cbAdiponectin, its multimers, and their distribution. cbAdiponectin concentrations are independently related to mAdiponectin levels and unrelated to the diagnosis of GDM. Maternal multimeric forms of adiponectin are independent predictors of the concentrations of cbAdiponectin and its multimeric forms at delivery.
  Diabetes care 09/2011; 34(11):2418-23. · 8.09 Impact Factor
• Article: The retinoic acid receptor-related orphan nuclear receptor γ1 (RORγ1): a novel player determinant of insulin sensitivity in morbid obesity.

  Francisco J Tinahones, Inmaculada Moreno-Santos, Joan Vendrell, M R Chacon, Lourdes Garrido-Sanchez, Eduardo García-Fuentes, Manuel Macias-González
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  ABSTRACT: The orphan nuclear receptors (ONRs), retinoic acid receptor-related orphan receptor γ-1 (RORγ1) and peroxisome proliferator-activated receptor γ-2 (PPARγ2), are central mediators controlling adipocyte (AD) differentiation. Through their distinct tissue distribution and specific target gene activation, ONRs control diverse aspects of fatty acid metabolism and insulin sensitivity. Adding further complexity, obesity begets resistance to insulin signals and can ultimately result in diabetes. In this study, we investigate whether there are differences in the RORγ1 and PPARγ2 expression in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbid obesity (MO) individuals either insulin resistant (high-IR MO) or insulin sensitivity (low-IR MO). Our results indicate for the first time in human the RORγ1 mRNA and protein expression levels and activation with coactivator, such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) were higher in the VAT from high-IR MO. In contrast, PPARγ2 expression and activation were higher in the VAT from low-IR MO. In this way, we have also found a positive association between RORγ1 mRNA and protein expression with many components of metabolic syndrome, with a strong dependence of insulin and HOMA(IR) index in VAT, but not in SAT. Our data suggest that RORγ1 may be added to the growing list of nuclear receptors in adipose tissue use to modulate the insulin resistance associated to the obesity. Measurement of RORγ1 and PPARγ2 in adipose tissue might be useful for evaluating the outcomes of various clinical interventions for obesity-related diabetes type II.
  Obesity 09/2011; 20(3):488-97. · 4.28 Impact Factor
• Article: Study of the potential association of adipose tissue GLP-1 receptor with obesity and insulin resistance.

  Joan Vendrell, Rajaa El Bekay, Belén Peral, Eduardo García-Fuentes, Anna Megia, Manuel Macias-Gonzalez, José Fernández Real, Yolanda Jimenez-Gomez, Xavier Escoté, Gisela Pachón, Rafael Simó, David M Selva, María M Malagón, Francisco J Tinahones
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  ABSTRACT: The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.
  Endocrinology 08/2011; 152(11):4072-9. · 4.46 Impact Factor
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  Available from: Alex Sánchez

  Article: CD14 modulates inflammation-driven insulin resistance.

  José Manuel Fernández-Real, Sofia Pérez del Pulgar, Elodie Luche, José Maria Moreno-Navarrete, Aurelie Waget, Matteo Serino, Eleonora Sorianello, Alex Sánchez-Pla, Francesc Carmona Pontaque, Joan Vendrell, Matilde R Chacón, Wifredo Ricart, Remy Burcelin, Antonio Zorzano
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  ABSTRACT: The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance. The effects of recombinant human soluble CD14 (rh-sCD14) on insulin sensitivity (clamp procedure) and adipose tissue gene expression were evaluated in wild-type (WT) mice, high fat-fed mice, ob/ob mice, and CD14 knockout (KO) mice. We also studied WT mice grafted with bone marrow stem cells from WT donor mice and CD14 KO mice. Finally, CD14 was evaluated in human adipose tissue and during differentiation of human preadipocytes. rh-sCD14 led to increased insulin action in WT mice, high-fat-fed mice, and ob/ob mice, but not in CD14 KO mice, in parallel to a marked change in the expression of 3,479 genes in adipose tissue. The changes in gene families related to lipid metabolism were most remarkable. WT mice grafted with bone marrow stem cells from WT donor mice became insulin resistant after a high-fat diet. Conversely, WT mice grafted with cells from CD14 KO mice resisted the occurrence of insulin resistance in parallel to decreased mesenteric adipose tissue inflammatory gene expression. Glucose intolerance did not worsen in CD14 KO mice grafted with bone marrow stem cells from high fat-fed WT mice when compared with recipient KO mice grafted with cells from CD14 KO donor mice. CD14 gene expression was increased in whole adipose tissue and adipocytes from obese humans and further increased after tumor necrosis factor-α. CD14 modulates adipose tissue inflammatory activity and insulin resistance.
  Diabetes 06/2011; 60(8):2179-86. · 8.29 Impact Factor
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  Available from: Joaquim Peraire

  Article: Lipodystrophy and insulin resistance in combination antiretroviral treated HIV-1-infected patients: implication of resistin.

  Xavier Escoté, Merce Miranda, Sergi Veloso, Pere Domingo, Carlos Alonso-Villaverde, Joaquim Peraire, Consuelo Viladés, Verónica Alba, Montserrat Olona, Antoni Castro, Miguel López-Dupla, Joan-Josep Sirvent, Vicente Vicente, Joan Vendrell, Cristóbal Richart, Francesc Vidal
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  ABSTRACT: Little information is available with respect to the involvement of resistin in lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with combination antiretroviral therapy (cART). We determined whether the resistin (rest) -420C>G single-nucleotide polymorphism and plasma resistin are associated with the development of lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with cART. The study group comprised 299 HIV-1-infected patients treated with a stable cART for at least 1 year (143 with lipodystrophy and 156 without) and 175 uninfected controls. Anthropometric, clinical, and metabolic variables were determined. Homeostasis model assessment for insulin resistance was used to evaluate insulin resistance. Plasma resistin levels were determined by enzyme-linked immunosorbent assay. The rest -420C>G was assessed using restriction fragment length polymorphism. Student t test, 1-way and 2-way analysis of variance, χ2 test, and Pearson and Spearman correlations were performed for statistical analysis. Genotypes containing the rest -420G variant allele were significantly more common in HIV-1-infected patients without lipodystrophy compared with those with lipodystrophy (P = 0.037). Infected patients had significantly greater plasma resistin levels than uninfected controls (P < 0.001). Among infected patients, plasma resistin levels were significantly lower in patients with lipodystrophy with respect to those without (P = 0.034). In infected patients, plasma resistin levels had a significant positive correlation with insulin and homeostasis model assessment for insulin resistance: P < 0.001 and P = 0.002 in the lipodystrophy subset and P = 0.002 and P = 0.03 in the nonlipodystrophy subset, respectively. In our cohort of white Spaniards, the rest -420C>G single-nucleotide polymorphism may be associated with cART-related lipodystrophy. Plasma resistin correlates with insulin resistance in infected patients with and without lipodystrophy.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2011; 57(1):16-23. · 4.43 Impact Factor
• Article: The stress-activated protein kinase Hog1 develops a critical role after resting state.

  Xavier Escoté, Merce Miranda, Boris Rodríguez-Porrata, Albert Mas, Ricardo Cordero, Francesc Posas, Joan Vendrell
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  ABSTRACT: Quiescence is an essential process in eukaryotes. Control of cell cycle progression by stress-activated protein kinases (SAPK) is critical for cell adaptation to extracellular stimuli. In yeast, activation of the HOG MAPK signalling pathway results in the control of cell cycle at several phases. In this manuscript, we describe the role of Hog1p modulating re-entry into cell cycle from a resting state. Cells deficient in Hog1p activation show a delay in entering the mitotic cell cycle from the stationary phase. Furthermore, a repressible Hog1p allele (Hog1AS) presents a comparable behaviour at this phase to the deleted strain. In addition, the role of Hog1p at the stationary phase exit is not related to loss of cell viability. Moreover, when cells enter the mitotic cell cycle after being in the stationary phase, Hog1p is rapidly activated and concentrates in the nucleus where it modifies the expression of several genes. Similar results are obtained in higher eukaryotic cells by activation of p38. Thus, these results reveal a novel role of the SAPK Hog1p in the control of cell cycle progression as cells leave a resting state.
  Molecular Microbiology 03/2011; 80(2):423-35. · 5.01 Impact Factor