Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals

J Biol Chem. 2019 Jul 5;294(27):10698-10707. doi: 10.1074/jbc.RA118.006956. Epub 2019 May 31.


Fatty acid esters of hydroxy fatty acids (FAHFAs) are a recently discovered class of biologically active lipids. Here we identify the linoleic acid ester of 13-hydroxy linoleic acid (13-LAHLA) as an anti-inflammatory lipid. An oat oil fraction and FAHFA-enriched extract from this fraction showed anti-inflammatory activity in a lipopolysaccharide-induced cytokine secretion assay. Structural studies identified three LAHLA isomers (15-, 13-, and 9-LAHLA) as being the most abundant FAHFAs in the oat oil fraction. Of these LAHLAs, 13-LAHLA is the most abundant LAHLA isomer in human serum after ingestion of liposomes made of fractionated oat oil, and it is also the most abundant endogenous LAHLA in mouse and human adipose tissue. As a result, we chemically synthesized 13-LAHLA for biological assays. 13-LAHLA suppresses lipopolysaccharide-stimulated secretion of cytokines and expression of pro-inflammatory genes. These studies identify LAHLAs as an evolutionarily conserved lipid with anti-inflammatory activity in mammalian cells.

Keywords: FAHFAs; LAHLAs; inflammation; lipid; lipid signaling; lipid structure; lipid synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry
  • Adipose Tissue / metabolism
  • Animals
  • Anti-Inflammatory Agents / analysis
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Avena / chemistry*
  • Avena / metabolism
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Cytokines / metabolism
  • Esters / chemistry*
  • Humans
  • Linoleic Acids / chemistry*
  • Lipopolysaccharides / toxicity
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mass Spectrometry
  • Mice
  • Plant Oils / chemistry
  • Plant Oils / pharmacology
  • RAW 264.7 Cells
  • Stereoisomerism


  • Anti-Inflammatory Agents
  • Cytokines
  • Esters
  • Linoleic Acids
  • Lipopolysaccharides
  • Plant Oils