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

Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14365-14375. doi: 10.1073/pnas.2005924117. Epub 2020 Jun 8.


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), lncFAO, 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.

Keywords: Long noncoding RNA; inflammation; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fatty Acids / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Inflammation / immunology*
  • Lipopolysaccharides / immunology
  • Macrophage Activation / genetics
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mitochondrial Trifunctional Protein, beta Subunit / genetics*
  • Mitochondrial Trifunctional Protein, beta Subunit / metabolism
  • Oxidation-Reduction
  • Primary Cell Culture
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Skin / immunology
  • Skin / injuries
  • Wound Healing / immunology


  • Fatty Acids
  • Lipopolysaccharides
  • RNA, Long Noncoding
  • Hadhb protein, mouse
  • Mitochondrial Trifunctional Protein, beta Subunit