RT Journal Article
SR Electronic
T1 Reducing RIP140 Expression in Macrophage Alters ATM Infiltration, Facilitates White Adipose Tissue Browning, and Prevents High-Fat Diet–Induced Insulin Resistance
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 4021
OP 4031
DO 10.2337/db14-0619
VO 63
IS 12
A1 Liu, Pu-Ste
A1 Lin, Yi-Wei
A1 Lee, Bomi
A1 McCrady-Spitzer, Shelly K.
A1 Levine, James A.
A1 Wei, Li-Na
YR 2014
UL http://diabetes.diabetesjournals.org/content/63/12/4021.abstract
AB 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.