title: Injecting engineered anti-inflammatory macrophages therapeutically induces white adipose tissue browning and improves diet-induced insulin resistance.
abstract: We recently exploited a transgenic approach to coerce macrophage anti-inflammatory M2 polarization in vivo by lowering Receptor Interacting Protein 140 (RIP140) level in macrophages (mφRIP140KD), which induced browning of white adipose tissue (WAT). In vitro, conditioned medium from cultured adipose tissue macrophages (ATMs) of mφRIP140KD mice could trigger preadipocytes' differentiation into beige cells. Here we describe a cell therapy for treating high fat diet (HFD)-induced insulin resistance (IR). Injecting M2 ATMs retrieved from the WAT of mφRIP140KD mice into HFD-fed obese adult wild-type mice effectively triggers their WAT browning, reduces their pro-inflammatory responses, and improves their insulin sensitivity. These data provide a proof-of-concept that delivering engineered anti-inflammatory macrophages can trigger white fat browning, stimulate whole-body thermogenesis, and reduce obesity-associated IR.
authors.affiliation: Department of Pharmacology; University of Minnesota Medical School ; Minneapolis, MN USA.
authors.forename: Pu-Ste
authors.initials: PS
authors.lastname: Liu
authors.affiliation: Department of Pharmacology; University of Minnesota Medical School ; Minneapolis, MN USA.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Department of Pharmacology; University of Minnesota Medical School ; Minneapolis, MN USA ; Minneapolis Medical Research Foundation; Hennepin County Medical Center ; Minneapolis, MN USA.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Burton
authors.affiliation: Department of Pharmacology; University of Minnesota Medical School ; Minneapolis, MN USA.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
keywords: (v)WAT, (visceral) white adipose tissue; ATM(s), adipose tissue macrophage(s); BAT, brown adipose tissue; FFA, free fatty acid; GTT, glucose tolerance test; HFD; HFD, high-fat diet; IL4, Interleukin 4; IR, insulin resistance; ITT, insulin tolerance test; KD, knockdown mice; M2 ATM; ND, normal diet; PBS, phosphate-buffered saline; RIP140; RIP140, Receptor Interacting Protein 140; SVF, stromal vascular fraction; TG, triglyceride; WT, wild-type mice; beige cells; browning; insulin resistance; macrophages; mφRIP140KD, macrophage-specific RIP140 knockdown mutation; obesity; preadipocyte differentiation