Gut Microbiota Interacts with Markers of Adipose Tissue Browning, Insulin Action and Plasma Acetate in Morbid Obesity

José María Moreno‐Navarrete, Matteo Serino, Vincent Blasco‐Baque, Vincent Azalbert, Richard H. Barton, Marina Cardellini, Jèssica Latorre, Francisco Ortega, Mònica Sabater‐Masdeu, Rémy Burcelin, Marc‐Emmanuel Dumas, Wifredo Ricart, Massimo Federici, José Manuel Fernández‐Real

To examine the potential relationship among gene expression markers of adipose tissue browning, gut microbiota and insulin sensitivity in humans. Gut microbiota composition and gene markers of browning were analysed in subcutaneous (SAT) and visceral (VAT) adipose tissue from morbidly obese subjects (n = 34). Plasma acetate was measured through (1) H NMR and insulin sensitivity using euglycemic hyperinsulinemic clamp. Subjects with insulin resistance showed an increase in the relative abundance (RA) of the phyla Bacteroidetes and Proteobacteria while RA of Firmicutes was decreased. In all subjects, Firmicutes RA was negatively correlated with HbA1c and fasting triglycerides, whereas Proteobacteria RA was negatively correlated with insulin sensitivity. Firmicutes RA was positively associated with markers of brown adipocytes (PRDM16, UCP1 and DIO2) in SAT, but not in VAT. Multivariate regression analysis indicated that Firmicutes RA contributed significantly to SAT PRDM16, UCP1 and DIO2 mRNA variance after controlling for age, BMI, HbA1c or insulin sensitivity. Interestingly, Firmicutes RA, specifically those bacteria belonging to Ruminococcaceae family, was positively associated with plasma acetate levels, which were also linked to SAT PRDM16 mRNA and insulin sensitivity. Gut microbiota composition is linked to adipose tissue browning and insulin action in morbidly obese subjects, possibly through circulating acetate. This article is protected by copyright. All rights reserved.