Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity.

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

Papel de la adiponectina en obesidad y diabetes tipo 2 / Role of adiponectine on obesity and diabetes type 2

Resumen: La adiponectina es una hormona sensibilizadora a la insulina y antiinflamatoria secretada por el tejido adiposo que tiene un inmenso potencial como objetivo terapéutico de una multitud de enfermedades relacionadas con la obesidad, incluida la diabetes tipo 2, la aterosclerosis y las enfermedades cardiovasculares. El gen de la adiponectina se encuentra en el cromosoma 3q27, un locus de susceptibilidad para la diabetes tipo 2 y los trastornos metabólicos. El aumento de las concentraciones circulantes de adiponectina se asocia con reducción del síndrome metabólico y las reducciones son muy predictivas del riesgo de diabetes. Se han hecho grandes esfuerzos para comprender cómo pueden elevarse las concentraciones de adiponectina. El complejo procesamiento postraduccional y la secreción de adiponectina proporciona un área rica en la que puede desarrollarse la manipulación farmacológica para aumentar las concentraciones de adiponectina en humanos. Las concentraciones circulantes de adiponectina se incrementan con muchos fármacos de administración común, como las estatinas, los inhibidores de la enzima convertidora de angiotensina y las tiazolidinedionas, lo que da una oportunidad importante para conocer los mecanismos que subyacen a sus efectos. Esta revisión describe la relación que existe entre la obesidad, la diabetes tipo 2 y la adiponectina, se discuten las funciones específicas en los tejidos y las células de la adiponectina, con insistencia en la regulación de las vías de señalización de adiponectina, así como las posibles vías de señalización implicadas en la regulación metabólica.

Abstract: Adiponectin is an insulin-sensitizing and anti-inflammatory fat cell hormone that has immense potential as a therapeutic target for a multitude of obesity-associated diseases including type 2 diabetes, atherosclerosis and cardiovascular diseases. The adiponectin gene is located in chromosome 3q27, a susceptibility locus for type 2 diabetes and metabolic disorders. Increased circulating levels of adiponectin are associated with improvement in the metabolic syndrome and reductions are strongly predictive of diabetes risk. Extensive efforts have been made to understand how adiponectin levels can be elevated. The complex posttranslational processing and secretion of adiponectin provides a rich area where pharmacologic manipulation may be developed to increase adiponectin levels in humans. Circulating adiponectin levels are increased by many commonly used drugs, such as statins, angiotensin converting enzyme inhibitors, and thiazolidinediones providing an important opportunity to gain insight into the mechanisms underlying their effects. This review describes the relationship among obesity, type 2 diabetes and adiponectin, we discuss the specific functions in tissues and cells of adiponectin, with emphasis on the regulation of adiponectin signaling pathways, as well as possible pathways of signaling involved in metabolic regulation.

Low serum levels of alpha1 anti-trypsin (α1-AT) and risk of airflow obstruction in non-primary α1-AT-deficient patients with compensated chronic liver disease.

BACKGROUND: Alpha1 anti-trypsin (α1-AT), a serine protease inhibitor synthesized in the liver, is a major circulating antiprotease that provides defense against proteolytic damage in several tissues. Its deficiency is associated with airflow obstruction. The present study aimed to explore the role of α1-AT as a biomarker of airflow performance in chronic liver disease (CLD). MATERIAL/METHODS: Serum α1-AT levels and lung function (spirometry) were evaluated in non-primary α1-AT-deficient, alcoholic CLD patients without evident respiratory limitations. RESULTS: Thirty-four patients with airflow obstruction (n=11), airflow restriction (n=12), and normal airflow (n=11, age-matched controls) were eligible. α1-AT was decreased in the airflow obstruction group. ROC-cutoff α1-AT=24 mg/dL effectively discriminated airflow obstruction (AUC=0.687) and was associated with a 10-fold higher risk (p=0.0007). CONCLUSIONS: Lower α1-AT increased the risk of airflow obstruction in CLD patients without primary α1-AT deficiency.

[Molecular markers: an important tool in the diagnosis, treatment and epidemiology of invasive aspergillosis]. / Marcadores moleculares: una herramienta importante en el diagnóstico, tratamiento y epidemiología de la aspergilosis invasora.

Increase in the incidence of invasive aspergillosis has represented a difficult problem for management of patients with this infection due to its high rate of mortality, limited knowledge concerning its diagnosis, and therapeutic practice. The difficulty in management of patients with aspergillosis initiates with detection of the fungus in the specimens of immunosuppressed patients infected with Aspergillus fumigatus; in addition, difficulty exists in terms of the development of resistance to antifungals as a consequence of their indiscriminate use in prophylactic and therapeutic practice and to ignorance concerning the epidemiological data of aspergillosis. With the aim of resolving these problems, molecular markers is employed at present with specific and accurate results. However, in Mexico, the use of molecular markers has not yet been implemented in the routine of intrahospital laboratories; despite the fact that these molecular markers has been widely referred in the literature, it is necessary for it to validated and standardized to ensure that the results obtained in any laboratory would be reliable and comparable. In the present review, we present an update on the usefulness of molecular markers in accurate identification of A. fumigatus, detection of resistance to antifugal triazoles, and epidemiological studies for establishing the necessary measures for prevention and control of aspergillosis.

El incremento en la incidencia de la aspergilosis invasora representa un grave problema para el tratamiento de pacientes con esta micosis, debido a su elevada tasa de mortalidad por deficiencias diagnósticas y terapéuticas. Éstas se han atribuido a la dificultad para detectar Aspergillus fumigatus, principal agente etiológico de esta micosis, en las muestras biológicas de pacientes inmunosuprimidos, que son los principales afectados por el hongo; además por la resistencia a los antifúngicos como consecuencia del uso incontrolado de éstos, a nivel profiláctico y terapéutico, y el desconocimiento de aspectos epidemiológicos de la aspergilosis. En la actualidad, para superar estas limitaciones se han empleado marcadores moleculares. En México su uso aún no está implementado en la rutina de los laboratorios intrahospitalarios, porque a pesar de que se han reportado ampliamente en la bibliografía, hace falta validarlos y estandarizarlos para asegurar que los resultados que se obtengan en cualquier laboratorio sean confiables y comparables. En este trabajo se presenta una revisión actualizada de la utilidad de los marcadores moleculares en la identificación certera de A. fumigatus en la detección de resistencia a los antifúngicos triazólicos y en estudios epidemiológicos para establecer las medidas necesarias en la prevención y control de la aspergilosis.