Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

Background: Obesity is a complex metabolic condition in strong association with various diseases, like type 2 diabetes, resulting in major public health and economic implications. Obesity is the result of environmental and genetic factors and their interactions, including genome-wide genetic interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model for human obesity, offering the possibility to study in-depth organ-level transcriptomic regulations of obesity, unfeasible in humans. Our aim was to reveal adipose tissue co-expression networks, pathways and transcriptional regulations of obesity using RNA Sequencing based systems biology approaches in a porcine model. Methods: We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results: WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P <0.001). Functional annotation identified pathways enlightening the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E(-7)), and immune-related complications (e. g. Natural killer cell mediated cytotoxity, P = 3.8E(-5); B cell receptor signaling pathway, P = 7.2E(-5)). Lemon-Tree identified three potential regulator genes, using confident scores, for the WGCNA module which was associated with osteoclast differentiation: CCR1, MSR1 and SI1 (probability scores respectively 95.30, 62.28, and 34.58). Moreover, detection of differentially connected genes identified various genes previously identified to be associated with obesity in humans and rodents, e.g. CSF1R and MARC2. Conclusions: To our knowledge, this is the first study to apply systems biology approaches using porcine adipose tissue RNA-Sequencing data in a genetically characterized porcine model for obesity. We revealed complex networks, pathways, candidate and regulatory genes related to obesity, confirming the complexity of obesity and its association with immune-related disorders and osteoporosis

A population-based study of the stratum corneum moisture

Thiago de Farias Pires,1 Ana Paula Azambuja,2 Andrea Roseli Van&ccedil;an Russo Horimoto,1 Mary Sanae Nakamura,2 Rafael de Oliveira Alvim,1 Jos&eacute; Eduardo Krieger,1 Alexandre Costa Pereira1 1Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of S&atilde;o Paulo Medical School, 2Natura Innovation and Product Technology Ltd., Cajamar, SP, Brazil Background: The stratum corneum (SC) has important functions as a bound-water modulator and a primary barrier of the human skin from the external environment. However, no large epidemiological study has quantified the relative importance of different exposures with regard to these functional properties. In this study, we have studied a large sample of individuals from the Brazilian population in order to understand the different relationships between the properties of SC and a number of demographic and self-perceived variables. Methods: One thousand three hundred and thirty-nine individuals from a rural Brazilian population, who were participants of a family-based study, were submitted to a cross-sectional examination of the SC moisture by capacitance using the Corneometer&reg; CM820 and investigated regarding environmental exposures, cosmetic use, and other physiological and epidemiological measurements. Self-perception-scaled questions about skin conditions were also applied. Results: We found significant associations between SC moisture and sex, age, high sun exposure, and sunscreen use frequency (P&lt;0.025). In specific studied sites, self-reported race and obesity were also found to show significant effects. Dry skin self-perception was also found to be highly correlated with the objective measurement of the skin. Other environmental effects on SC moisture are also reported. Keywords: investigative dermatology, stratum corneum moisture, Corneometer, sun exposure, familial data modelin

Intervenção nutricional padronizada em pacientes hipoglicêmicos hospitalizados

A ingestão de carboidratos de rápida absorção (CRA) pode ser útil para o aumento sérico de glicose. Neste contexto, os   principais objetivos foram avaliar a eficácia e a aplicabilidade   da intervenção nutricional em situações hipoglicêmicas apresentadas por pacientes conscientes, com dieta via oral e internados em hospital geral. Setenta e seis pacientes foram elegíveis e a hipoglicemia foi definida como nível de glicemia capilar ≥ 50 até ≤ 70mg/dL. A intervenção nutricional constituiu na oferta de 15 a 24 gramas de CRA. Houve a conferência da glicemia capilar após 15-20 minutos da intervenção. A taxa de efetividade da intervenção nutricional foi de 97,6%, durante o período de estudo. Conclui-se que a administração de CRA, um método não invasivo, foi aplicável em unidades de um hospital geral e foi potencialmente eficaz na restauração da glicemia capilar em pacientes hipoglicêmicos com dieta via oral e conscientes

Cohort profile: the Baependi Heart Study--a family-based, highly admixed cohort study in a rural Brazilian town

Purpose Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits. Participants Probands were recruited in Baependi, a small rural town in the state of Minas Gerais, Brazil, following by first-degree and then increasingly more distant relatives. The first follow-up wave took place in 2010, and the second in 2016. At baseline, the study evaluated 1691 individuals across 95 families. Cross-sectional data have been collected for 2239 participants. Findings to date Environmental and lifestyle factors and measures relevant to cardiovascular health have been reported. Having expanded beyond cardiovascular health outcomes, the phenotype datasets now include genetics, biochemistry, anthropometry, mental health, sleep and circadian rhythms. Many of these have yielded heritability estimates, and a shared genetic background of anxiety and depression has recently been published. In spite of universal access to electricity, the population has been found to be strongly shifted towards morningness compared with metropolitan areas. Future plans A new follow-up, marking 10 years of the study, is ongoing in 2016, in which data are collected as in 2010 (with the exception of the neuropsychiatric protocol). In addition to this, a novel questionnaire package collecting information about intelligence, personality and spirituality is being planned. The data set on circadian rhythms and sleep will be amended through additional questionnaires, actimetry, home sleep EEG recording and dim light melatonin onset (DLMO) analysis. Finally, the anthropometric measures will be expanded by adding three-dimensional facial photography, voice recording and anatomical brain MRI

Static cut-points of hypertension and increased arterial stiffness in children and adolescents: The International Childhood Vascular Function Evaluation Consortium

Pediatric elevated blood pressure (BP) and hypertension are usually defined using traditional BP tables at the 90th and 95th percentiles, respectively, based on sex, age, and height, which are cumbersome to use in clinical practice. The authors aimed to assess the performance of the static cut-points (120/80 mm Hg and 130/80 mm Hg for defining elevated BP and hypertension for adolescents, respectively; and 110/70 mm Hg and 120/80 mm Hg for children, respectively) in predicting increased arterial stiffness. Using data from five population-based cross-sectional studies conducted in Brazil, China, Korea, and New Zealand, a total of 2546 children and adolescents aged 6-17 years were included. Increased arterial stiffness was defined as pulse wave velocity ≥sex-specific, age-specific, and study population-specific 90th percentile. Compared to youth with normal BP, those with hypertension defined using the 2017 American Academy of Pediatrics guideline (hereafter referred to as "percentile-based cut-points") and the static cut-points were at similar risk of increased arterial stiffness, with odds ratios and 95% confidence intervals of 2.35 (1.74-3.17) and 3.07 (2.20-4.28), respectively. Area under the receiver operating characteristic curve and net reclassification improvement methods confirmed the similar performance of static cut-points and percentile-based cut-points (P for difference > .05). In conclusion, the static cut-points performed similarly well when compared with the percentile-based cut-points in predicting childhood increased arterial stiffness. Use of static cut-points to define hypertension in childhood might simplify identification of children with abnormal BP in clinical practice

The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men

BACKGROUND: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined. METHODS: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease. RESULTS: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01-1.59). CONCLUSIONS: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males