title: Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice.
abstract: Adipose tissue macrophage (ATM)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT) can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival.
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.
authors.forename: Jongkil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.|Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Kunho
authors.initials: K
authors.lastname: Chung
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.|Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Changseon
authors.initials: C
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Beloor
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.
authors.forename: Irfan
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.
authors.forename: Nahyeon
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Priti
authors.initials: P
authors.lastname: Kumar
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