Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults
Author:
Gallegos-Cabriales Esther C.ORCID, Rodriguez-Ayala ErnestoORCID, Laviada-Molina Hugo A.ORCID, Nava-Gonzalez Edna J.ORCID, Salinas-Osornio Rocío A., Orozco LorenaORCID, Leal-Berumen IreneORCID, Castillo-Pineda Juan Carlos, Gonzalez-Lopez Laura, Escudero-Lourdes ClaudiaORCID, Cornejo-Barrera Judith, Escalante-Araiza FabiolaORCID, Huerta-Avila Eira E.ORCID, Buenfil-Rello Fatima A.ORCID, Peschard Vanessa-GiselleORCID, Silva EliudORCID, Veloz-Garza Rosa A., Martinez-Hernandez AngelicaORCID, Barajas-Olmos Francisco M.ORCID, Molina-Segui FernandaORCID, Gonzalez-Ramirez LuciaORCID, Arjona-Villicaña Ruy D.ORCID, Hernandez-Escalante Victor M.ORCID, Gaytan-Saucedo Janeth F.ORCID, Vaquera Zoila, Acebo-Martinez MonicaORCID, Murillo-Ramirez Areli, Diaz-Tena Sara P., Figueroa-Nuñez BenignoORCID, Valencia-Rendon Melesio E., Garzon-Zamora Rafael, Viveros-Paredes Juan ManuelORCID, Valdovinos-Chavez Salvador B., Comuzzie Anthony GORCID, Haack KarinORCID, Thorsell Ashley A., Han XianlinORCID, Cole Shelley A.ORCID, Bastarrachea Raul A.ORCID
Abstract
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.
Funder
National Institute of Diabetes and Digestive and Kidney Diseases
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology
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