Moderate SIRT1 overexpression protects against brown adipose tissue inflammation

Objective: Metainflammation is a chronic low-grade inflammatory state induced by obesity and associated comorbidities, including peripheral insulin resistance. Brown adipose tissue (BAT), a therapeutic target against obesity, is an insulin target tissue sensitive to inflammation. Therefore, it is demanding to find strategies to protect BAT against the effects of inflammation in energy balance. In this study we have explored the impact of moderate Sirtuin 1 (SIRT1) overexpression in insulin sensitivity and β-adrenergic responses in BAT and brown adipocytes (BA) under pro-inflammatory conditions. Methods: The effect of inflammation in BAT functionality was studied in obese db/db mice and lean wild-type (WT) mice or mice with moderate overexpression of SIRT1 (SIRT1Tg+) injected a low dose of bacterial lipopolysaccharide (LPS) to mimic endotoxemia. We also conducted studies in differentiated BA (BA-WT and BA-SIRT1Tg+) exposed to a macrophagederived pro-inflammatory conditioned medium (CM) to evaluate the protection of SIRT1 overexpression in insulin signaling and glucose uptake, mitochondrial respiration, fatty acid oxidation (FAO), as well as norepinephrine (NE)-mediated-modulation of uncoupling protein-1 (UCP-1) expression. Results: BAT from db/db mice was susceptible to metabolic inflammation manifested by activation of pro-inflammatory signaling cascades, increased pro-inflammatory gene expression, tissue-specific insulin resistance and reduced UCP-1 expression. Impairment of insulin and noradrenergic responses were also found in lean WT mice upon LPS injection. By contrast, BAT from mice with moderate overexpression of SIRT1 (SIRT1Tg+) was protected against LPSinduced activation of pro-inflammatory signaling, insulin resistance and defective thermogenicrelated responses upon cold exposure. Importantly, the drop of triiodothyronine (T3) levels both in circulation and intra-BAT after exposure of WT mice to LPS and cold was markedly attenuated in SIRT1Tg+ mice. In vitro experiments in BA from the two genotypes revealed that upon differentiation with a T3-enriched medium and subsequent exposure to a macrophagederived pro-inflammatory CM, only BA-SIRT1Tg+ fully recovered insulin and noradrenergic responses. Conclusion: This study has unraveled the benefit of moderate overexpression of SIRT1 to confer protection against defective insulin and β-adrenergic responses caused by inflammation in BAT. Our results have potential therapeutic value proposing combinatorial therapies of BATspecific thyromimetics and SIRT1 activators to combat metainflammation in this tissue

No association of the dopamine D2 receptor genetic bilocus score (rs1800497/rs1799732) on food addiction and food reinforcement in Chilean adults

Purpose: Different systems regulate food intake. In the reward system, dopamine (DA) is the main neurotransmitter, and a variety of genetic variants (rs1799732 and rs1800497) are associated with addiction. Addiction is a highly polygenic disease, where each allelic variant adds a small amount of vulnerability. Polymorphisms rs1799732 and rs1800497 are associated with eating behavior and hedonic hunger, but links to food addiction remain unclear.Aim: To evaluate the association between the bilocus profile (rs1799732-rs1800497) of the dopaminergic pathway with food reinforcement and food addiction in Chilean adults.Methods: A cross-sectional study recruited a convenience sample of 97 obese, 25 overweight, and 99 normal-weight adults (18–35 years). Anthropometric measurements were performed by standard procedures and eating behavior was assessed using the: Food Reinforcement Value Questionnaire (FRVQ) and Yale Food Addiction scale (YFAS). The DRD2 genotypes were determined by TaqMan assays (rs1800497 and rs1799732). A bilocus composite score was calculated.Results: In the normal weight group, individuals who were heterozygous for the rs1977932 variant (G/del) showed higher body weight (p-value 0.01) and abdominal circumference (p-value 0.01) compared to those who were homozygous (G/G). When analyzing rs1800497, a significant difference in BMI was observed for the normal weight group (p-value 0.02) where heterozygous showed higher BMI. In the obese group, homozygous A1/A1 showed higher BMI in comparison to A1/A2 and A2/A2 (p-value 0.03). Also, a significant difference in food reinforcement was observed in the rs1800497, where homozygous for the variant (A1A1) show less reinforcement (p-value 0.01).In relation to the bilocus score in the total sample, 11% showed “very low dopaminergic signaling”, 24.4% were “under”, 49.7% showed “intermediate signaling”, 12.7% showed “high” and 1.4% showed “very high”. No significant genotypic differences were observed in food reinforcement and food addiction by bilocus score.Conclusions: The results indicate that the genetic variants rs1799732 and rs1800497 (Taq1A) were associated with anthropometric measurements but not with food addiction or food reinforcement in Chilean university students. These results suggest that other genotypes, such as rs4680 and rs6277, which affect DA signaling capacity through a multilocus composite score, should be studied. Level V: Evidence obtained from a cross-sectional descriptive study

Low miR-222 expression in human visceral adipose tissue is associated with insulin resistance and PTEN and p53 mRNA levels

Introduction: The aim of this is study was to analyse the expression of miR-193b, miR-378, miR-Let7-d, and miR-222 in human visceral adipose tissue (VAT), as well as their association with obesity, insulin resistance (IR), and their role in the regulation of genes controlling adipose tissue homeostasis, including adipocytokines, the phosphatase and tension homologue (PTEN), and tumour protein 53 (p53). Material and methods: VAT was obtained from normal-weight (NW), overweight, and obese (OW/OB) subjects with and without IR. Stem-loop RT-qPCR was used to evaluate miRNA expression levels. miRTarBase 4.0, miRWalk, and DIANA-TarBase v8 were used for prediction of validated target gene of the miRNA analysed. A qPCR was used to evaluate PTEN, p53, leptin (LEP), and adiponectin (ADIPOQ) mRNA. Results: miR-222 was lower in IR subjects, and miR-222 and miR-378 negatively correlated with HOMA-IR. PTEN and p53 are miR-222 direct targets according to databases. mRNA expression of PTEN and p53 was lower in OW/OB subjects with and without IR, compared to NW group and its levels positively associated with miR-222. Additionally, p53 and PTEN are positively associated with serum leptin levels. On the other hand, miR-193b and miR-378 negatively correlated with serum leptin but not with mRNA levels. Moreover, miR-Let-7d negatively correlated with serum adiponectin but not with adiponectin mRNA levels. Conclusions: Lower miR-222 levels are associated with IR, and PTEN and p53 expression; the implication of these genes in adipose tissue homeostasis needs more research

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans¿ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Adaptación y análisis factorial del cuestionario de conducta de alimentación del adulto (AEBQ) en idioma español

El Cuestionario de Conducta de Alimentación de Adultos (AEBQ, por su sigla en inglés derivada de Adult Eating Behavior Questionnaire) es una de las herramientas psicométricas más usadas para evaluar la conducta de alimentación. El objetivo de este estudio fue adaptar y analizar factorialmente la versión en idioma español del AEBQ. El cuestionario adaptado al idioma español se aplicó en un estudio piloto de 50 voluntarias universitarias entre 20 y 30 años de edad. Se utilizó la técnica de análisis factorial para reducir la dimensionalidad de los datos y evaluar preliminarmente su estructura. Se usó la estadística alfa de Cronbach para explorar la consistencia interna del cuestionario adaptado. El análisis factorial reveló una estructura de 8 factores que explican el 82,8 % de la variación de los datos, lo que es concordante con el número de dimensiones de la conducta de alimentación publicada para el AEBQ original. La consistencia interna fue alta, con valores de la estadística α de Cronbach entre 0,77 y 0,91 para las 8 dimensiones consideradas. En conclusión, la versión adaptada al idioma español del AEBQ presenta una razonable concordancia en su estructura de datos con el cuestionario publicado originalmente en inglés, así como una adecuada consistencia interna. Se deben realizar futuros estudios de mayor tamaño muestral que incluyan participantes de diferentes grupos de edad, sexo y estado nutricional.The Adult Eating Behavior Questionnaire (AEBQ) is one the most used psychometric tool to evaluate eating behavior. The objective of this study was to adapt and analyze the factorial structure of the Spanish version of the AEBQ. The adapted questionnaire was submitted to a non-probabilistic sample of 50 female university students aged 20 - 30 years old. A factorial analysis was used to preliminary assess data structure, while Cronbach's alpha statistic was used to assess internal consistency. Factor analysis revealed an8-factor structure explaining 82,8% of data variation, which is concordant with data structure of the original AEBQ. The internal consistency was high, with Cronbach's α between 0.77 and 0.91 for all eating behavior dimensions. In conclusion, this Spanish version of the AEBQ shows adequate concordance with the factor structure of the originally published AEBQ, as well as high internal consistency. Future studies will evaluate the validity of the questionnaire in different subpopulation groups according to gender, age or nutritional status