Increased Expression of Resistin in MicroRNA-155-Deficient White Adipose Tissues May Be a Possible Driver of Metabolically Healthy Obesity Transition to Classical Obesity

• Main Authors: Candice Johnson, Charles Drummer, Anthony Virtue, Tracy Gao, Susu Wu, Miguel Hernandez, Lexy Singh, Hong Wang, Xiao-Feng Yang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-10-01
• Series: Frontiers in Physiology
• Subjects: microRNAs; atherosclerosis; diabetes; fatty liver disease; obesity; resistin
• Online Access: https://www.frontiersin.org/article/10.3389/fphys.2018.01297/full

We reported that microRNA-155 (miR-155) deficiency in ApoE-/- mice yields a novel metabolically healthy obese (MHO) model, which exhibits improved atherosclerosis but results in obesity, non-alcoholic fatty liver disease (NAFLD) without insulin resistance. Using experimental data mining approaches combined with experiments, we found that, among 109 miRNAs, miR-155, and miR-221 are significantly modulated in all four hyperlipidemia-related diseases (HRDs), namely atherosclerosis, NAFLD, obesity and type II diabetes (T2DM). MiR-155 is significantly upregulated in atherosclerosis and decreased in other HRDs. MiR-221 is increased in three HRDs but reduced in obesity. These findings led to our new classification of types I and II MHOs, which are regulated by miR-221 and miR-155, respectively. Western blots showed that the proinflammatory adipokine, resistin, is significantly increased in white adipose tissues (WAT) of the MHO mice, revealing our newly proposed, miR-155-suppressed “secondary wave inflammatory state (SWIS),” characteristic of MHO transition to classical obesity (CO). Taken together, we are first to show that MHO may have heterogeneity in comorbidities, and is therefore classified into type I, and type II MHOs; and that increased expression of resistin in miR-155-/- white adipose tissues may be a driver for SWIS in MHO transition to CO. Our findings provide novel insights into the pathogenesis of MHO, MHO transition to CO, hyperlipidemic pathways related to cancer, and new therapeutic targets.