Yang, Shuo and Wang, Bingwei and Humphries, Fiachra and Hogan, Andrew and O'Shea, Donal and Moynagh, Paul N. (2014) The E3 Ubiquitin Ligase Pellino3 Protects against Obesity-Induced Inflammation and Insulin Resistance. Immunity, 41 (6). ISSN 1097-4180

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Abstract

Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1β (IL-1β) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced expression of the E3 ubiquitin ligase Pellino3 in human abdominal adipose tissue from obese subjects and in adipose tissue of mice fed a high-fat diet and showing signs of insulin resistance. Pellino3-deficient mice demonstrated exacerbated high-fat-diet-induced inflammation, IL-1β expression, and insulin resistance. Mechanistically, Pellino3 negatively regulated TNF receptor associated 6 (TRAF6)-mediated ubiquitination and stabilization of hypoxia-inducible factor 1α (HIF1α), resulting in reduced HIF1α-induced expression of IL-1β. Our studies identify a regulatory mechanism controlling diet-induced insulin resistance by highlighting a critical role for Pellino3 in regulating IL-1β expression with implications for diseases like type 2 diabetes.

Item Type:	Article
Keywords:	E3 Ubiquitin Ligase Pellino3; Obesity-Induced Inflammation; Insulin Resistance;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	11033
Identification Number:	https://doi.org/10.1016/j.immuni.2014.11.013
Depositing User:	Professor Paul Moynagh
Date Deposited:	10 Sep 2019 16:10
Journal or Publication Title:	Immunity
Publisher:	Elsevier
Refereed:	Yes
Funders:	Science Foundation Ireland (SFI)
URI:	https://www.sciencedirect.com/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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