IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling
Katharina Timper, Jesse Lee Denson, Sophie Marie Steculorum, Christian Heilinger, Linda Engström-Ruud, Claudia Maria Wunderlich, Stefan Rose-John, F Thomas Wunderlich, Jens Claus Brüning, Katharina Timper, Jesse Lee Denson, Sophie Marie Steculorum, Christian Heilinger, Linda Engström-Ruud, Claudia Maria Wunderlich, Stefan Rose-John, F Thomas Wunderlich, Jens Claus Brüning
Abstract
Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance.
Keywords: CNS; energy homeostasis; glucose homeostasis; interleukin-6; interleukin-6 trans-signaling; obesity.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed