A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation

Yukiteru Nakayama, Katsuhito Fujiu, Ryuzaburo Yuki, Yumiko Oishi, Masaki Suimye Morioka, Takayuki Isagawa, Jun Matsuda, Tsukasa Oshima, Takumi Matsubara, Junichi Sugita, Fujimi Kudo, Atsushi Kaneda (+5 others)
2020 Proceedings of the National Academy of Sciences of the United States of America  
Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA),
more » ... cFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages. lncFAO is induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chi monocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found that lncFAO directly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO. lncFAO deletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism, lncFAO acts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.
doi:10.1073/pnas.2005924117 pmid:32513690 fatcat:wgmp3us4vfd4bbxozcwhfgsqcq