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

Music Convocation

https://dc.ewu.edu/music_performances/1768/thumbnail.jp

Estimación de biomasa y carbono en dos especies arboreas en La Sierra Nevada, México

Se generaron dos ecuaciones para determinar biomasa y carbono en Pinus montezumae y Alnus jorullensis H. B. K. ssp. jorullensis especies de importancia ecológica de los bosques de la Sierra Nevada en el Estado de México. Las ecuaciones que se determinaron son de la forma Y= bXk, donde Y es el contenido de biomasa o de carbono (kg) y X el diámetro normal (DN) en cm. Para estimar los valores b y k del modelo para cada especie, se utilizaron 15 árboles de Pinus montezumae y 16 de Alnus jorullensis ssp. jorullensis. En Pinus montezumae el mayor porcentaje de biomasa 77.07 % se estimó en el fuste incluido el tocón, mientras que en las ramas y el follaje presentó 8.45 y 9.01%, respectivamente, con la biomasa y el DN de los árboles se obtuvo el ajuste de los parámetros b y k del modelo propuesto (B= 0.013 DN3.0462) con una R2= 0.9909. Para el caso de Alnus jorullensis ssp. jorullensis de la misma forma el mayor porcentaje de biomasa 63.77% se estimó en el fuste incluido el tocón, mientras que en las ramas y el follaje presentó 20.99 y 11.46%, respectivamente; con la biomasa y el DN de los árboles se obtuvo el ajuste de los parámetros b y k del modelo propuesto (B= 0.0195 DN2.7519) con una R2= 0.9311. Después de analizar el contenido de carbono en las muestra de cada especie, se ajustaron las ecuaciones para Pinus montezumae C= 0.0065DN3.0484, con una R2= 0.9914, mientras que para Alnus jorullensis ssp. jorullensis C= 0.009DN2.7522con una R2= 0.9313.Two equations were generated for determining the biomass and carbon in Pinus montezumae and Alnus jorullensis HBK ssp. jorullensis of ecological important species of the forests of the Sierra Nevada in the State of Mexico. The equations were determined are of the form Y= bXk, where Y is the biomass content or carbon (kg) and X normal diameter (DN) in cm. For estimating the model and k values for each species, Pinus montezumae 15 trees and 16 Alnusjorullensis ssp. jorullensis were used. In Pinus montezumae the highest percentage of biomass was estimated at 77.07% including the stem stump, while the branches and foliage showed 8.45 and 9.01%, respectively, biomass and DN trees the adjustment is obtained by k parameters of the proposed model (B= 0.013 DN3.0462) with R2= 0.9909. For the case of Alnus jorullensis ssp. jorullensis the same as the highest percentage of biomass was estimated at 63.77% including the stem stump, while the branches and foliage showed 20.99 and 11.46%, respectively; with biomass and tree DN setting the parameters of the proposed model by k (B= 0.0195 DN2.7519) with R2= 0.9311 was obtained. After analyzing the carbon content in the sample of each species, the equations for Pinus montezumae C= 0.0065DN3.0484, with R2= 0.9914, while for Alnus jorullensis ssp jorullensis was adjusted. C= 0.009DN2.7522 con an R2= 0.9313

Senior Composition Recital of Alexander Wolfe

https://dc.ewu.edu/music_performances/1722/thumbnail.jp

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) 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