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

• Main Authors: Ernesto Rodriguez-Ayala, Esther C. Gallegos-Cabrales, Laura Gonzalez-Lopez, Hugo A. Laviada-Molina, Rocio A. Salinas-Osornio, Edna J. Nava-Gonzalez, Irene Leal-Berumen, Claudia Escudero-Lourdes, Fabiola Escalante-Araiza, Fatima A. Buenfil-Rello, Vanessa-Giselle Peschard, Antonio Laviada-Nagel, Eliud Silva, Rosa A. Veloz-Garza, Angelica Martinez-Hernandez, Francisco M. Barajas-Olmos, Fernanda Molina-Segui, Lucia Gonzalez-Ramirez, Rebeca Espadas-Olivera, Ricardo Lopez-Muñoz, Ruy D. Arjona-Villicaña, Victor M. Hernandez-Escalante, Martha E. Rodriguez-Arellano, Janeth F. Gaytan-Saucedo, Zoila Vaquera, Monica Acebo-Martinez, Judith Cornejo-Barrera, Huertas-Quintero Jancy Andrea, Juan Carlos Castillo-Pineda, Areli Murillo-Ramirez, Sara P. Diaz-Tena, Benigno Figueroa-Nuñez, Melesio E. Valencia-Rendon, Rafael Garzon-Zamora, Juan Manuel Viveros-Paredes, José Ángeles-Chimal, Jesús Santa-Olalla Tapia, José M. Remes-Troche, Salvador B. Valdovinos-Chavez, Eira E. Huerta-Avila, Juan Carlos Lopez-Alvarenga, Anthony G Comuzzie, Karin Haack, Xianlin Han, Lorena Orozco, Susan Weintraub, Jack W. Kent, Shelley A. Cole, Raul A. Bastarrachea
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2020-01-01
• Series: Adipocyte
• Subjects: adipose tissue dysfunction; immunometabolism; postprandial tissue biopsies; non-coding micrornas; shotgun lipidomics
• Online Access: http://dx.doi.org/10.1080/21623945.2020.1743116

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.