title: Reducing RIP140 expression in macrophage alters ATM infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance.
abstract: Adipose tissue macrophage (ATM) recruitment and activation play a critical role in obesity-induced inflammation and insulin resistance (IR). The mechanism regulating ATM activation and infiltration remains unclear. In this study, we found receptor interacting protein 140 (RIP140) can regulate the dynamics of ATM that contribute to adipose tissue remodeling. A high-fat diet (HFD) elevates RIP140 expression in macrophages. We generated mice with RIP140 knockdown in macrophages using transgenic and bone marrow transplantation procedures to blunt HFD-induced elevation in RIP140. We detected significant white adipose tissue (WAT) browning and improved systemic insulin sensitivity in these mice, particularly under an HFD feeding. These mice have decreased circulating monocyte population and altered ATM profile in WAT (a dramatic reduction in inflammatory classically activated macrophages [M1] and expansion in alternatively activated macrophages [M2]), which could improve HFD-induced IR. These studies suggest that reducing RIP140 expression in monocytes/macrophages can be a new therapeutic strategy in treating HFD-induced and inflammation-related diseases.
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN.
authors: Pu-Ste
authors: PS
authors: Liu
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN.
authors: Yi-Wei
authors: YW
authors: Lin
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN.
authors: Bomi
authors: B
authors: Lee
authors: Endocrine Research Unit, Mayo Clinic, Rochester, MN.
authors: Shelly K
authors: SK
authors: McCrady-Spitzer
authors: Endocrine Research Unit, Mayo Clinic, Rochester, MN.
authors: James A
authors: JA
authors: Levine
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN weixx009@umn.edu.
authors: Li-Na
authors: LN
authors: Wei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000276:immunology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D055786:Gene Knockout Techniques; D007333:Insulin Resistance / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1