The Role and Potential Therapeutic Implications of the Fibroblast Growth Factors in Energy Balance and Type 2 Diabetes.

PURPOSE OF REVIEW: Obesity and its associated metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have become attractive targets in the treatment of metabolic diseases. This review summarizes their most important functions as well as FGF-based therapies for the treatment of obesity and type 2 diabetes (T2D). RECENT FINDINGS: Recent studies demonstrate that circulating levels of FGF19 are reduced in obesity. In fact, exogenous FGF19 administration is associated with a reduction in food intake as well as with improvements in glycaemia. In contrast, FGF21 levels are elevated in subjects with abdominal obesity, insulin resistance and T2D, probably representing a compensatory response. Additionally, elevated levels of circulating FGF23 in individuals with obesity and T2D are reported in most clinical studies. Finally, increased FGF1 levels in obese patients associated with adipogenesis have been described. FGFs constitute important molecules in the treatment of metabolic diseases due to their beneficial effects on glucose and lipid metabolism. Among all members, FGF19 and FGF21 have demonstrated the ability to improve glucose, lipid and energy homeostasis, along with FGF1, which was recently discovered to have beneficial effects on metabolic homeostasis. Additionally, FGF23 may also play a role in insulin resistance or energy homeostasis beyond mineral metabolism control. These results highlight the relevant use of FGFs as potential biomarkers for the early diagnosis of metabolic diseases. In this regard, notable progress has been made in the development of FGF-based therapies and different approaches are being tested in different clinical trials. However, further studies are needed to determine their potential therapeutic use in the treatment of obesity and obesity-related comorbidities.

Comparative effects of gastric bypass and sleeve gastrectomy on plasma osteopontin concentrations in humans.

BACKGROUND: Bariatric surgery (BS) has proven to be an effective treatment for morbid obesity. Osteopontin (OPN) is a proinflammatory cytokine involved in the development of obesity. The aim of our study was to determine the effect of weight loss following BS on circulating levels of OPN in humans. METHODS: Body composition and circulating concentrations of OPN and markers of bone metabolism were determined in obese patients who underwent Roux-en-Y gastric bypass (RYGB; n = 40) or sleeve gastrectomy (SG; n = 11). RESULTS: Patients who underwent RYGB or SG showed decreased body weight (P < 0.001) and body fat percentage (P < 0.001) as well as lower insulin resistance. However, plasma OPN levels were significantly increased after RYGB (P < 0.001) but remained unchanged following SG (P = 0.152). Patients who underwent RYGB also showed significantly increased C-terminal telopeptide of type-I collagen (ICTP) (P < 0.01) and osteocalcin (P < 0.001) while bone mineral density tended to decrease (P = 0.086). Moreover, OPN concentrations were positively correlated with the bone resorption marker ICTP after surgery. On the other hand, patients who underwent SG showed significantly increased ICTP levels (P < 0.05), and the change in OPN was positively correlated with the change in ICTP and negatively with the change in vitamin D after surgery (P < 0.05). CONCLUSIONS: RYGB increased circulating OPN levels, while they remained unaltered after SG. The increase in OPN levels after RYGB could be related to the increased bone resorption in relation to its well-known effects on bone of this malabsorptive procedure in comparison to the merely restrictive SG.

Bioceramic versus traditional biomaterials for endodontic sealers according to the ideal properties.

Odontology, as a scientific discipline, continuously collaborates with biomaterials engineering to enhance treatment characteristics and patients' satisfaction. Endodontics, a specialized field of dentistry, focuses on the study, diagnosis, prevention, and treatment of dental disorders affecting the dental pulp, root, and surrounding tissues. A critical aspect of endodontic treatment involves the careful selection of an appropriate endodontic sealer for clinical use, as it significantly influences treatment outcomes. Traditional sealers, such as zinc oxide-eugenol, fatty acid, salicylate, epoxy resin, silicone, and methacrylate resin systems, have been extensively used for decades. However, advancements in endodontics have given rise to bioceramic-based sealers, offering improved properties and addressing new challenges in endodontic therapy. In this review, a classification of these materials and their ideal properties are presented to provide evidence-based guidance to clinicians. Physicochemical properties, including sealing ability, stability over time and space, as well as biological properties such as biocompatibility and antibacterial characteristics, along with cost-effectiveness, are essential factors influencing clinicians' decisions based on individual patient evaluations.

PD-1/PD-L1 axis: implications in immune regulation, cancer progression, and translational applications.

The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management.

Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity.

PURPOSE: Six-transmembrane epithelial antigen of prostate (STEAP)-4 and neutrophil gelatinase-associated lipocalin (NGAL) are novel adipokines related to iron homeostasis with potential roles in insulin resistance and inflammation. The aim of the present work was to evaluate the effect of obesity and iron status on gene expression levels of STEAP-4 and NGAL in visceral adipose tissue (VAT) and its implication in inflammation. METHODS: VAT biopsies obtained from 53 subjects were used in the study. Real-time PCR and Western-blot were performed to quantify the levels of STEAP4 and NGAL in VAT as well as the association with other genes implicated in inflammatory pathways. Circulating ferritin and free iron concentrations were also determined. RESULTS: Obese patients exhibited significantly increased STEAP4 and NGAL mRNA expression levels (P < 0.001) compared to lean subjects. Protein expression levels of NGAL (P < 0.05) and STEAP4 were also higher in the visceral fat depot of obese patients, although protein levels of STEAP4 did not reach statistical significance. A negative correlation (P < 0.05) between free iron concentrations and gene expression levels of both STEAP4 and NGAL was found, while circulating ferritin concentrations were positively correlated (P < 0.05) with NGAL mRNA after body fat (BF) adjustment. Furthermore, a significant positive association between STEAP4 and NGAL gene expression levels with inflammatory markers was also detected (P < 0.01). CONCLUSION: These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.

Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review).

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and accounts for >90% of all oral cancers. Despite advances in diagnostic procedures and therapeutic interventions, overall survival has not improved significantly in recent decades, primarily due to late diagnosis, locoregional recurrence and treatment resistance. Identifying reliable biomarkers for early detection, prognosis evaluation and treatment response prediction is critical for improving clinical outcomes in patients with OSCC. In the present review, the prognostic and predictive utility of circulating biomarkers, such as circulating tumour cells, serological biomarkers and histological and genetic biomarkers, were explored in the context of OSCC. In addition, the potential role of immune checkpoints in the treatment of OSCC was highlighted and the rapidly evolving field of liquid biopsy and its potential to revolutionize diagnosis, prognosis evaluation and treatment were examined. The existing evidence for the clinical utility of these biomarkers was critically evaluated and the challenges and limitations associated with their introduction into routine clinical practice were addressed. In conclusion, the present review highlights the promising role of biomarkers in improving the current understanding of the pathogenesis of OSCC and offers potential avenues for improving patient care through personalized medicine approaches.

AIF1: Function and Connection with Inflammatory Diseases.

Macrophages are a type of immune cell distributed throughout all tissues of an organism. Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein linked to the activation of macrophages. AIF1 is a key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several cell type-specific functions. AIF1 plays important roles in the development of several diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases and neurological disorders, and in transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.

Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss.

Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity-associated comorbidities.

Adverse effects, pharmacological interactions, and cardiovascular drugs in COVID-19 treatment.

In severe coronavirus disease (COVID)-19 patients, an extraordinary systemic inflammatory response is seen. It could impact in multiple organ disorders, specially a severe myocardial injury, an acute myocarditis results in focal or global myocardial inflammation and necrosis. Those events can be present in healthy subjects or cardiovascular (CV) patients. It is clinically associated with ventricular dysfunction exacerbation or worsening and tachyarrhythmias. It is also related to a poor outcome for CV patients with ischemic heart disease, hypertensión, and heart failure. COVID-19 patients require multiple and complex treatment that alleviates symptoms, the vast variety of agents interacts with diseases and CV drugs. Our purpose is to correlate in guidance synopsis: Adverse effects, pharmacological interactions, and CV drugs in COVID-19 treatment.

En pacientes con COVID-19 grave se ha observado una extraordinaria respuesta inflamatoria sistémica. Este impacto se traduce en múltiples trastornos de órganos, especialmente cardíacos, por lesión miocárdica grave, miocarditis aguda que resulta en inflamación focal o miocárdica global, necrosis cardiaca. Estos tremendos eventos son observados en sujetos sanos como pacientes cardiovasculares. Clínicamente asociados con nueva presentación o empeoramiento de la disfunción ventricular y taquiarritmias. Relacionado a un predictor principal de malos resultado en pacientes cardiovasculares (CV), especialmente en aquellos con cardiopatía isquémica, hipertensión e insuficiencia cardíaca. Los enfermos con COVID-19 requieren múltiples y complejos tratamientos que alivien los síntomas, esta gran variedad de agentes interactúa con enfermedades y medicamentos CV. Nuestro propósito es correlacionar, en una guía sinóptica: efectos adversos, interacciones farmacológicas y fármacos cardiovasculares en el tratamiento del COVID-19.

Benzo[b]thiophene-6-carboxamide 1,1-dioxides: inhibitors of human cancer cell growth at nanomolar concentrations.

Benzo[b]thiophenesulfonamide 1,1-dioxide derivatives (BTS) were described as candidate antineoplastic drugs. In the hope of finding new compounds with improved antitumour activity and reduced toxicity, we have designed and synthesized a small series of benzo[b]thiophene-6-carboxamide 1,1-dioxide derivatives (BTC) structurally related with the best reported BTS. Growth inhibition of HTB-54, CCRF-CEM and HeLa tumour cells lines at nanomolar concentrations was exhibited by some of the BTC. Hydrophobic substituents on the carboxamide group increased cytotoxicity but substitution by a hydroxy group diminished it, thus pointing to the electronic density on benzo[b]thiophene nucleus as a determinant factor. The process of cell death induced by BTC derivatives was further analyzed in CCRF-CEM cells, where these compounds induced apoptosis in a time and dose-dependent manner and cell cycle arrest at S phase. BTC derivatives also induced a significant increase in intracellular ROS levels in this cell line. Previous treatment of the cells with the antioxidant N-acetyl-cysteine abrogated the induction of apoptosis by BTC indicating that ROS generation is a previous event required to trigger the BTC induced apoptotic process.

RIP140 gene and protein expression levels are downregulated in visceral adipose tissue in human morbid obesity.

BACKGROUND: Receptor-interacting protein 140 (RIP140) is a corepressor for nuclear receptors with an important role in the inhibition of energy expenditure. Rip140-knockout mice are lean and resistant to diet-induced obesity due to an increase in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. The aim of the present work was to evaluate the effect of morbid obesity on gene and protein expression levels of RIP140 in visceral adipose tissue (VAT). METHODS: VAT biopsies obtained from 17 subjects were used in the study. Patients were classified as lean (body mass index [BMI]=21.8+/-1.3 kg/m2) or obese (BMI=48.2+/-2.6 kg/m2). Reverse transcription polymerase chain reaction and Western blot analyses were performed to quantify the expression levels of RIP140 in VAT. We also analyzed glucose and lipid profile as well as some inflammatory factors. RESULTS: Obese patients exhibited significantly lower RIP140 mRNA expression levels compared to lean subjects (lean=1.00+/-0.17 arbitrary units, obese=0.65+/-0.18 arbitrary units; P<0.05). Protein expression of RIP140 followed the same trend, being significantly higher in lean volunteers (lean=1.00+/-0.18 arbitrary units, obese=0.45+/-0.11 arbitrary units; P<0.05). Furthermore, a significant negative correlation was found between RIP140 protein levels and both BMI (rho=-0.85; P<0.001) and body fat percentage (rho=-0.88; P<0.001). CONCLUSIONS: The lower gene and protein expression levels of RIP140 in obese subjects may suggest a compensatory mechanism in order to favor energy expenditure and reduce fat accumulation in obesity states.

IAOx induces the SUR phenotype and differential signalling from IAA under different types of nitrogen nutrition in Medicago truncatula roots.

Indole-3-acetaldoxime (IAOx) is a particularly relevant molecule as an intermediate in the pathway for tryptophan-dependent auxin biosynthesis. The role of IAOx in growth-signalling and root phenotype is poorly studied in cruciferous plants and mostly unknown in non-cruciferous plants. We synthesized IAOx and applied it to M. truncatula plants grown axenically with NO3-, NH4+ or urea as the sole nitrogen source. During 14 days of growth, we demonstrated that IAOx induced an increase in the number of lateral roots, especially under NH4+ nutrition, while elongation of the main root was inhibited. This phenotype is similar to the phenotype known as "superroot" previously described in SUR1- and SUR2-defective Arabidopsis mutants. The effect of IAOx, IAA or the combination of both on the root phenotype was different and dependent on the type of N-nutrition. Our results also showed the endogenous importance of IAOx in a legume plant in relation to IAA metabolism, and suggested IAOx long-distance transport depending on the nitrogen source provided. Finally, our results point out to CYP71A as the major responsible enzymes for IAA synthesis from IAOx, while they exclude indole-3-acetaldehyde oxidases.

Pretreatment and enzymatic hydrolysis for the efficient production of glucose and furfural from wheat straw, pine and poplar chips.

A flexible approach to a two-step Biorefinery for the production of glucose and furfural from three different feedstocks is presented. Pretreatment conditions were selected to drive the production towards the generation of glucose or furfural. Harsh pretreatment conditions produced solids with highly accessible glycan contents for the enzymatic hydrolysis with 100% glucose yields when wheat straw or poplar chips were used as feedstock. Mild conditions afforded xylan-rich hydrolysates that could be efficiently transformed to furfural, either under conventional or microwave heating in biphasic media. Yields for the transformation of xylan from feedstocks ranged between 45% and 90% depending on the feedstock, the thermal pretreatment and the cyclodehydration conditions. Up to 12.6 kg of glucose and materials and 2.5 kg of furfural can be produced starting from 50 kg of biomass. A new analytical methodology based on 13C NMR that provided good quality analytical results is also presented.

Clinimetric analysis of heart failure in Mexican patients.

Heart failure (HF) is a syndrome characterized basically by a circulatory deficit to cover the metabolic and energetic demands of the body. This condition has a broad spectrum in its clinical presentation, affects the quality of life significantly, impacts the family/social environment, and generates a great demand for health services. The purpose of this research is to report the situational diagnose of patients with HF in Mexico. We evaluated 292 patients, 70.2% were men. Average age was 56.7 ± 14.3 years. Ischemic heart disease is the main etiology (98 patients, 33.9%) followed by hypertensive (22.6%) and idiopathic (23.3%) heart disease. The associated clinical background was obesity (31.1%), systemic hypertension (36.7%), myocardial infarction (26.4%), and dyslipidemia (15.1%). The most common symptom was stress dyspnea (41.4%) and jugular vein engorgement at physical examination (32.5%). Anemia was observed in 1% of patients. The average left ventricular ejection fraction was 29.2 ± 10.6%. Sinus rhythm was the most frequently detected in 84.9%. 19.9% of patients had an implantable cardioverter-defibrillator or cardiac resynchronization therapy. 13.7% of patients with QRS > 130 ms. In our population, the meta-analysis global group in chronic heart failure risk score calculated was 16.8 ± 5.7 and for EMPHASIS 3.3 ± 1.5. We observed that age at presentation in HF in this analysis is at least 10 years younger than in other reports. The grade of obesity takes relevance in our group. The association of anemia and HF in Mexico is rare.

La insuficiencia cardiaca es un síndrome caracterizado fundamentalmente por un déficit circulatorio para cubrir las demandas metabólicas y energéticas del organismo. Esta entidad tiene un amplio espectro en su presentación clínica, afecta de manera significativa la calidad de vida, impacta en el entorno familiar/social y genera una gran demanda de los servicios de salud. El propósito de esta investigación es reportar el diagnóstico situacional de pacientes con insuficiencia cardiaca (IC) en México. Evaluamos 292 enfermos, 70.2% eran hombres. Con edad promedio 56.7 ± 14.3 años. La principal etiología es la cardiopatía isquémica (33.9%), seguida de la hipertensiva (22.6%) e idiopática (23.3%). Los antecedentes clínicos asociados fueron: obesidad (31.1%), hipertensión arterial sistémica (36.7%), infarto al miocardio (26.4%) y dislipidemia (15.1%). El síntoma con mayor presentación fue la disnea de esfuerzos (41.4%) y a la exploración física la ingurgitación yugular (32.5%). Se observó anemia en 1% de los enfermos. La fracción de expulsión del ventrículo izquierdo (FEVI) promedio fue de 29.2 + 10.6%. El ritmo sinusal fue el más frecuentemente detectado en 84.9%. El 19.9% de los pacientes tenían instalado un desfibrilador automático implantable (DAI) o tratamiento de resincronización cardiaca (TRC). El 13.7% de los enfermos con QRS mayor de 130 ms. El riesgo (MAGGIC) calculado en nuestro grupo poblacional fue de 16.8 ± 5.7 y para EMPHASIS 3.3 ± 1.5. Observamos que la edad de presentación de la IC en el presente análisis es menor por 10 años en comparación con otros reportes. El grado de obesidad toma relevancia en nuestro grupo. La asociación de anemia e IC en México es poco frecuente.

Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation.

OBJECTIVE: Caveolin-1 (CAV-1) plays important roles in many aspects of cellular biology, including vesicular transport, cholesterol homeostasis and signal transduction. The aim of the present study was to explore gene expression levels of CAV-1 in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to analyse its potential implication in the inflammatory state associated with obesity. DESIGN AND METHODS: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) obtained from 15 females were used in the study. Patients were classified as lean (BMI 20.8 +/- 1.0 kg/m(2)) or obese (BMI 50.5 +/- 2.6 kg/m(2)). The obese group was further subclassified as normoglycaemic (NG) or patients with T2DM. Anthropometric measurements as well as circulating metabolites, hormones and adipokines were determined. Real-time polymerase chain reaction (PCR) analyses were performed to quantify transcript levels of CAV-1 and monocyte chemoattractant protein (MCP-1). RESULTS: The presence of CAV-1 protein was detected in VAT and SAT by immunohistochemistry. Both obese NG and with T2DM patients exhibited significantly higher CAV-1 expression levels in VAT and SAT compared with lean subjects (P < 0.05). No differences between obese NG and T2DM patients were observed in VAT. However, obese T2DM patients were found to have higher CAV-1 expression levels in SAT (P < 0.05) compared with obese NG patients. A significant correlation was found between CAV-1 mRNA expression levels in VAT and different circulating inflammatory markers such as sialic acid (SA) (P < 0.001) and fibrinogen (P < 0.001) as well as with MCP1 mRNA expression (P < 0.05). CONCLUSION: Our findings show for the first time the upregulation of mRNA CAV-1 expression levels in VAT and SAT of obese NG and obese T2DM patients compared with lean controls, suggesting a role for CAV-1 in obesity and T2DM development. The association with different inflammatory markers further suggests an implication of CAV-1 in the low-grade inflammation accompanying obesity.

Influence of morbid obesity and insulin resistance on gene expression levels of AQP7 in visceral adipose tissue and AQP9 in liver.

BACKGROUND: Glycerol production and its efflux from adipocytes to the liver are key to modulate lipid and glucose homeostasis. Aquaporin 7 (AQP7) is an aquaglyceroporin that acts as the adipose glycerol channel, whereas aquaporin 9 (AQP9) is the specific channel operating in the liver. The aim of the present work was to evaluate the effect of obesity and type 2 diabetes mellitus (T2DM) on gene expression levels of AQP7 in visceral adipose tissue (VAT) and AQP9 in liver. METHODS: VAT and liver biopsies obtained from 20 women were used in the study. Patients were classified as lean or obese with the last group being further subclassified as normoglycemic (NG), patients with impaired glucose tolerance (IGT), or with T2DM. Anthropometric measurements as well as circulating metabolites, hormones, and adipokines were determined. Real-time polymerase chain reaction analyses were performed to quantify transcript levels of AQP7 in VAT and AQP9 in the liver. RESULTS: Gene expression levels of AQP7 in VAT showed a tendency toward an increase (P = 0.065) in obese patients (both NG and T2DM) compared to lean subjects. AQP9 showed a significant downregulation in the hepatic biopsies obtained from obese T2DM patients compared to obese NG and IGT patients (P = 0.028). CONCLUSION: The tendency toward an elevation of mRNA expression of VAT AQP7 in obesity together with the decreased hepatic AQP9 expression observed in obese T2DM subjects suggests a potential role in facilitating glycerol release from adipose tissue and reducing glycerol entry into hepatocytes in obesity and T2DM, respectively.

Clinical usefulness of abdominal bioimpedance (ViScan) in the determination of visceral fat and its application in the diagnosis and management of obesity and its comorbidities.

BACKGROUND & AIMS: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomography (CT). Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with CT and its clinical usefulness in the management of obesity. METHODS: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m2 to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. RESULTS: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm2, and then with lower precision with increasing body mass, exhibiting a moderate-high correlation with CT-VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. CONCLUSIONS: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01055626 and NCT01572090.

Plasma osteopontin levels and expression in adipose tissue are increased in obesity.

CONTEXT: Obesity acts as a cardiovascular risk factor by mechanisms that are not fully understood. Osteopontin (OPN) is a proinflammatory mediator involved in tissue remodeling that plays a role in atherosclerosis and diabetes. OBJECTIVE: The aim of the present study was to compare the circulating concentrations of OPN and its mRNA expression in omental adipose tissue of lean, overweight, and obese individuals and to analyze the effect of weight loss. SUBJECTS AND METHODS: Plasma concentrations of OPN were measured in 77 volunteers. OPN mRNA expression in omental adipose tissue obtained from 12 women was quantified by real-time PCR. In addition, the concentrations of OPN in 12 obese men were measured before and after weight loss following a dietetic program. SETTING: The study was conducted at a University Hospital. RESULTS: Obese and overweight patients exhibited significantly increased circulating OPN concentrations as compared with lean subjects (obese 72.6 +/- 28.5, overweight 68.2 +/- 20.8, lean 42.7 +/- 27.9 ng/ml; P < 0.001). A significant positive correlation was found between OPN levels and body fat (r = 0.45; P < 0.0001). Obese individuals showed significantly increased (P < 0.05) mRNA expression of OPN in omental adipose tissue as compared with lean volunteers, which was further increased in obese diabetic patients. Diet-induced weight loss significantly decreased OPN concentrations from 64.7 +/- 22.1 to 36.6 +/- 20.1 ng/ml (P = 0.006). CONCLUSIONS: These findings represent the first observation that plasma OPN and mRNA expression of OPN in omental adipose tissue are increased in overweight/obese patients with the latter being further elevated in obesity-associated diabetes. Moreover, weight loss reduces OPN concentrations, which may contribute to the beneficial effects accompanying weight reduction. Measurement of OPN might be useful for evaluating the outcomes of various clinical interventions for obesity-related cardiovascular diseases.

Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass.

BACKGROUND: Obesity and obesity-associated type 2 diabetes mellitus (T2DM) are frequently related to a low-grade chronic inflammatory state, which increases the risk of developing cardiovascular diseases. The aim of the present work was to evaluate the effect of obesity and T2DM on the concentrations of pro-inflammatory factors and to study the effect of weight loss after Roux-en-Y gastric bypass (RYGBP). METHODS: Plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), serum amyloid A (SAA) and sialic acid (SA) were measured in 25 female volunteers. The concentrations of these cytokines were determined in 14 female obese patients before and after weight loss following RYGBP. Additionally, visceral adipose tissue (VAT) obtained from 15 females was used to quantify expression levels of MCP-1 and CD68 by Real-Time PCR. RESULTS: Both obese normoglycemic (NG) and T2DM groups exhibited significantly higher MCP-1 (P < 0.05), TNF-alpha (P < 0.01), SAA (P < 0.05) and SA (P < 0.05) concentrations, compared to the lean group. No differences were found between obese NG and obese T2DM subjects. A significant positive correlation was found between body fat percentage (BF) and all inflammatory markers (P < 0.05) studied. MCP-1 expression levels in VAT were upregulated in obese NG (P = 0.008) and obese T2DM (P = 0.032) patients compared to lean subjects, but no additional detrimental effect of T2DM was observed between both obese groups. After weight loss, SAA (P < 0.001) and SA (P < 0.05) concentrations diminished, whereas circulating levels of MCP-1 showed a tendency to decrease (P = 0.093) and TNF-alpha did not change. CONCLUSION: The present findings suggest that elevated pro-inflammatory cytokine levels found in obese patients relate mainly to obesity rather than to T2DM. Moreover, surgery-induced weight loss reduces circulating concentrations of key pro-inflammatory factors, which contribute to the improvement in the cardiovascular co-morbidity following excess weight loss.

Increased cardiovascular risk markers in obesity are associated with body adiposity: role of leptin.

Epidemiological studies have shown that obesity is associated with increased blood concentrations of proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), and von Willebrand factor (vWF). We analyzed the association of these markers with percentage of body fat (BF), and the influence of leptin in a cross-sectional study of 1,089 subjects (366 men) aged 44 (34-53) [median (interquartile range)] years, who were classified as obese or nonobese according to BF estimated by whole-body air displacement plethysmography. Obesity was defined as BF >or= 25% in men and >or= 35% in women. Compared with non-obese subjects (mean +/- SD), obese patients had higher concentrations of fibrinogen (312 +/- 78 vs. 342 +/- 81 mg/dl, P < 0.001), CRP (0.41 +/- 0.75 vs. 0.75 +/- 1.04 mg/l, P = 0.014), vWF (107 +/- 29 vs. 123 +/- 55%, P < 0.001), and leptin (10.4 +/- 6.5 vs. 37.5 +/- 26.1 ng/ml, P < 0.0001). A positive correlation was observed between BF and fibrinogen (r = 0.266; P < 0.0001), logCRP (r = 0.409; P < 0.0001), and vWF (r = 206; P < 0.0001). Leptin was correlated with fibrinogen (r = 0.219, P < 0.0001), logCRP (r = 0., P < 0.0001), and vWF (r = 0.124, P = 0.002), but the statistical significance was lost after including BF in adjusted-correlation and multivariate analysis, suggesting that they are not regulated by leptin per se. In conclusion, the obesity-associated increase in the circulating concentrations of fibrinogen, CRP, and vWF is highly associated to BF and apparently not determined by leptin.