Adipose tissue macrophages (ATMs) recruitment and activation play a critical role in obesity-induced inflammation and insulin resistance (IR). 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 contributes to adipose tissue remodeling. A high fat diet (HFD) elevates RIP140 expression in macrophage. 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 a HFD feeding. These mice have decreased circulating monocyte population and altered ATM profile in WAT (a dramatic reduction in inflammatory M1 and expansion in M2 macrophage), 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.
- Received April 17, 2014.
- Accepted June 20, 2014.
- © 2014 by the American Diabetes Association.
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