Replication of integrative data analysis for adipose tissue dysfunction, low-grade inflammation, postprandial responses and omics signatures in symptom-free adults

Esther C. Gallegos-Cabriales, Ernesto Rodriguez-Ayala, Hugo A. Laviada-Molina, Edna J. Nava-Gonzalez, Rocío A. Salinas-Osornio, Lorena Orozco, Irene Leal-Berumen, Juan Carlos Castillo-Pineda, Laura Gonzalez-Lopez, Claudia Escudero-Lourdes, Judith Cornejo-Barrera, Fabiola Escalante-Araiza, Eira E. Huerta-Avila, Fatima A. Buenfil-Rello, Vanessa Giselle Peschard, Eliud Silva, Rosa A. Veloz-Garza, Angelica Martinez-Hernandez, Francisco M. Barajas-Olmos, Fernanda Molina-SeguiLucia Gonzalez-Ramirez, Ruy D. Arjona-Villicaña, Victor M. Hernandez-Escalante, Janeth F. Gaytan-Saucedo, Zoila Vaquera, Monica Acebo-Martinez, Areli Murillo-Ramirez, Sara P. Diaz-Tena, Benigno Figueroa-Nuñez, Melesio E. Valencia-Rendon, Rafael Garzon-Zamora, Juan Manuel Viveros-Paredes, Salvador B. Valdovinos-Chavez, Anthony G Comuzzie, Karin Haack, Ashley A. Thorsell, Xianlin Han, Shelley A. Cole, Raul A. Bastarrachea

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1342
JournalBiology
Volume10
Issue number12
DOIs
StatePublished - Dec 2021

Keywords

  • Adipose tissue dysfunction
  • Fat and muscle tissue biopsies
  • Low-grade chronic subclinical inflammation
  • Metabolically healthy/unhealthy phenotype
  • OMICs molecular signatures
  • Postprandial inflammatory response
  • Symptom-free volunteers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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