AIMS: In obesity, chronic low-grade inflammation and overproduction of reactive oxygen species (ROS) in fat contribute to the development of metabolic syndrome. Suppression of inflammation and ROS production in fat may attenuate the metabolic syndrome. Activation of mineralocorticoid receptor (MR) promotes inflammation in heart, kidney, and vasculature via ROS generation. However, the significance of MR in fat remains elusive. Here we investigated whether MR blockade attenuates obesity-related insulin resistance and improves adipocyte dysfunction. METHODS AND RESULTS: Obese ob/ob and db/db mice were treated with eplerenone, a MR antagonist, for 3 weeks. 3T3-L1 adipocytes were treated with aldosterone or H2O2, with and without eplerenone or MR-siRNA. High levels of MR mRNA were detected in adipose tissue of obese ob/ob and db/db mice. Eplerenone treatment significantly reduced insulin resistance, suppressed macrophage infiltration and ROS production in adipose tissues, and corrected the mRNA levels of obesity-related genes in obese mice. In 3T3-L1 adipocytes, aldosterone and H2O2 increased intracellular ROS levels and MR blockade inhibited such increases. H2O2 and aldosterone resulted in dysregulation of mRNAs of various genes related to ROS and cytokines, whereas MR blockade corrected such changes. CONCLUSION: MR blockade attenuates obesity-related insulin resistance partly through reduction of fat ROS production, inflammatory process, and induction of cytokines.
AIMS: In obesity, chronic low-grade inflammation and overproduction of reactive oxygen species (ROS) in fat contribute to the development of metabolic syndrome. Suppression of inflammation and ROS production in fat may attenuate the metabolic syndrome. Activation of mineralocorticoid receptor (MR) promotes inflammation in heart, kidney, and vasculature via ROS generation. However, the significance of MR in fat remains elusive. Here we investigated whether MR blockade attenuates obesity-related insulin resistance and improves adipocyte dysfunction. METHODS AND RESULTS:Obese ob/ob and db/db mice were treated with eplerenone, a MR antagonist, for 3 weeks. 3T3-L1 adipocytes were treated with aldosterone or H2O2, with and without eplerenone or MR-siRNA. High levels of MR mRNA were detected in adipose tissue of obese ob/ob and db/db mice. Eplerenone treatment significantly reduced insulin resistance, suppressed macrophage infiltration and ROS production in adipose tissues, and corrected the mRNA levels of obesity-related genes in obesemice. In 3T3-L1 adipocytes, aldosterone and H2O2 increased intracellular ROS levels and MR blockade inhibited such increases. H2O2 and aldosterone resulted in dysregulation of mRNAs of various genes related to ROS and cytokines, whereas MR blockade corrected such changes. CONCLUSION:MR blockade attenuates obesity-related insulin resistance partly through reduction of fat ROS production, inflammatory process, and induction of cytokines.
Authors: Margarita Pizarro; Nancy Solís; Pablo Quintero; Francisco Barrera; Daniel Cabrera; Pamela Rojas-de Santiago; Juan P Arab; Oslando Padilla; Juan C Roa; Han Moshage; Alexander Wree; Eugenia Inzaugarat; Ariel E Feldstein; Carlos E Fardella; Rene Baudrand; Arnoldo Riquelme; Marco Arrese Journal: Liver Int Date: 2015-02-23 Impact factor: 5.828
Authors: Jennifer N Cooper; Linda Fried; Ping Tepper; Emma Barinas-Mitchell; Molly B Conroy; Rhobert W Evans; Maria Mori Brooks; Genevieve A Woodard; Kim Sutton-Tyrrell Journal: Hypertens Res Date: 2013-05-09 Impact factor: 3.872
Authors: Jessica L Pierce; Ke-Hong Ding; Jianrui Xu; Anuj K Sharma; Kanglun Yu; Natalia Del Mazo Arbona; Zuleika Rodriguez-Santos; Paul Bernard; Wendy B Bollag; Maribeth H Johnson; Mark W Hamrick; Dana L Begun; Xing M Shi; Carlos M Isales; Meghan E McGee-Lawrence Journal: J Endocrinol Date: 2019-07-01 Impact factor: 4.286