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.

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.

MR blockade attenuates obesity-related insulin resistance partly through reduction of fat ROS production, inflammatory process, and induction of cytokines.