GRP94 Regulates M1 Macrophage Polarization and Insulin Resistance

Overview

Journal Am J Physiol Endocrinol Metab

Publisher American Physiological Society

Specialties Endocrinology
Physiology

Date 2020 Mar 26

PMID 32208002

Citations 10

Authors

Lili Song

Do-Sung Kim

Wenyu Gou

Jingjing Wang

Ping Wang

Zhiguo Wei

Bei Liu

Zihai Li

Kemian Gou

Hongjun Wang

Affiliations

Soon will be listed here.

Abstract

Macrophage polarization contributes to obesity-induced insulin resistance. Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER) chaperone specialized for folding and quality control of secreted and membrane proteins. To determine the role of GRP94 in macrophage polarization and insulin resistance, macrophage-specific GRP94 conditional knockout (KO) mice were challenged with a high-fat diet (HFD). Glucose tolerance, insulin sensitivity, and macrophage composition were compared with control mice. KO mice showed better glucose tolerance and increased insulin sensitivity. Adipose tissues from HFD-KO mice contained lower numbers of M1 macrophages, with lower expression of M1 macrophage markers, than wild-type (WT) mice. In vitro, WT adipocytes cocultured with KO macrophages retained insulin sensitivity, whereas those cultured with WT macrophages did not. In addition, compared with WT bone marrow-derived macrophages (BMDMs), BMDMs from GRP94 KO mice exhibited lower expression of M1 macrophage marker genes following stimulation with LPS or IFN-γ, and exhibited partially increased expression of M2 macrophage marker genes following stimulation with interleukin-4. These findings identify GRP94 as a novel regulator of M1 macrophage polarization and insulin resistance and inflammation.

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