Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals

Prevalencia de caries, gingivitis y maloclusiones en escolares de Ciudad Victoria, Tamaulipas y su relación con el estado nutricional

ResumenObjetivoEstimar la prevalencia de caries, gingivitis y maloclusiones en escolares de Ciudad Victoria, Tamaulipas y determinar su relación con el estado nutricional.MetodologíaSe realizó un estudio transversal comparativo en 402 escolares entre 7 y 12 años de edad los cuales contaban con la medición de su composición corporal, seleccionados aleatoriamente del listado del estudio «Obesidad en la población menor de 30 años de Tamaulipas: efectos sobre la salud, tratamiento y prevención» que se lleva a cabo en este hospital. Previo consentimiento por escrito, a todos ellos se les realizó un examen bucal, determinando la presencia de caries dental, gingivitis y maloclusiones según la OMS. Para el análisis estadístico, la base de datos electrónica se transfirió al programa STATA versión 9.0.ResultadosEl 50 % de los escolares nunca había acudido a una consulta dental, 36.2% tenían sobrepeso y obesidad, la prevalencia de caries fue de 87%, de gingivitis de 63% y de maloclusiones de 33%, el índice ceo-d de 2.97 y el CPO-D de 3.08. El análisis multivariado mostró relación entre el índice ceo-d con la edad (p = 0.00), con el sobrepeso y obesidad y con las maloclusiones (p = 0.016), así como relación entre la edad con la gingivitis (p = 0.01) y las maloclusiones (p = 0.042).ConclusionesLa prevalencia de caries y maloclusiones es similar a la de otros estudios en el país; en cambio, la gingivitis se presenta con mayor frecuencia en nuestra casuística, la relación más significativa es entre el índice ceo-d y el sobrepeso y obesidad.AbstractAimAssessment of caries, gingivitis and malocclusion prevalence in school-age children in the city of Ciudad Victoria, Tamaulipas, Mexico and determination of its relationship with their nutritional status.MethodologyA comparative, cross-sectional study was conducted on 402 school-age children (ages 7-12 years). These children could exhibit measurement of body composition. Children were randomly selected from the study list of «Obesity in Tamaulipas’ under 30 population, effects on health, treatment and prevention» conducted in this hospital. All subjects provided written consent, there after, oral examination was performed in order to determine, according to WHO parameters, presence of dental caries, gingivitis and malocclusions. Version 9.0 of STRATA program was used to conduct statistical analysis.Results50% of school age children had never attended a dental office. 32.2% were overweight or obese. Caries prevalence was 87%, gingivitis was present in 63% of all cases, and malocclusions were present in 33% of patients. Ceo-d index was 2.97 and CPO-D was 3.08. Multivariate analysis revealed relationship between the ceo-d index with age (p = 0.00), with overweigh and obesity and with malocclusions (p = 0.016) as well as relationship between age and gingivitis (p = 0.01) and age and malocclusion (p = 0.042).ConclusionsMalocclusion and caries prevalence resulted similar to that observed in other studies performed in Mexico. Nevertheless, gingivitis was more frequent. In our casuistry; the most significant relationship was that found between ceo-d index with overweight and obesity