title: M1-M2 balancing act in white adipose tissue browning - a new role for RIP140.
abstract: A "Holy Grail" sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophages that migrate into adipose deposits. The coregulator, Receptor Interacting Protein 140 (RIP140), plays a key role in regulating this communication. In mice on a high-fat diet, the level of RIP140 in macrophages is dramatically elevated to activate their inflammatory M1 polarization and enhance their recruitment into WAT, facilitating IR. Conversely, lowering the level of RIP140 in macrophages not only reduces M1 macrophages but also expands alternatively polarized, anti-inflammatory M2 macrophages, triggering white adipose tissue browning, fat burning, and restoration of insulin sensitivity. This suggests a potential therapeutic strategy for reversing IR, obesity, and atherosclerotic or even cosmetic fat deposits: therapeutic browning of white adipose deposits by diminishing RIP140 levels in macrophages.
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; HFD, high-fat diet; IR, insulin resistance; ND, normal diet; RIP140; RIP140, Receptor Interacting Protein 140; WT (wild-type mice); brown adipose tissue; inflammation; insulin resistance; macrophage polarization; metabolism; white adipose tissue