Deletion of class A scavenger receptor deteriorates obesity-induced insulin resistance in adipose tissue.

Abstract

Chronic low-grade inflammation, particularly in the adipose tissue, orchestrates obesity-induced insulin resistance. In this process, polarized activation of macrophages plays a crucial role. However, how macrophages contribute to insulin resistance remains obscure. Class A scavenger receptor (SR-A) is a pattern recognition receptor primarily expressed in macrophages. Through a combination of in vivo and in vitro studies, we report here that deletion of SR-A resulted in reduced insulin sensitivity in obese mice. The anti-inflammatory virtue of SR-A was accomplished by favoring M2 macrophage polarization in adipose tissue. Moreover, we demonstrate that lysophosphatidylcholine (LPC) served as an obesity-related endogenous ligand for SR-A promoting M2 macrophage polarization by activation of signal transducer and activator of transcription 6 signaling. These data have unraveled a clear mechanistic link between insulin resistance and inflammation mediated by the LPC/SR-A pathway in macrophages.

• Authors: Xudong Zhu, Guijuan Zong, Liu Zhu, Yuchen Jiang, Ke Ma, Hanwen Zhang, Yan Zhang, Hui Bai, Qing Yang, Jingjing Ben, Xiaoyu Li, Yong Xu, Qi Chen
• Journal: Diabetes (Diabetes) Vol. 63 Issue 2 Pg. 562-77 (Feb 2014) ISSN: 1939-327X [Electronic] United States
• PMID: 24170693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lysophosphatidylcholines
• Scavenger Receptors, Class A

Topics

• Adipose Tissue (metabolism)
• Animals
• Bone Marrow Transplantation
• Cells, Cultured
• Insulin Resistance (physiology)
• Lysophosphatidylcholines (metabolism)
• Macrophages, Peritoneal (physiology)
• Mice
• Mice, Knockout
• Obesity (complications)
• Scavenger Receptors, Class A (genetics, metabolism)