Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice

Nat Commun. 2013;4:2563. doi: 10.1038/ncomms3563.


Despite the established role of alveolar type II epithelial cells for the maintenance of pulmonary function, little is known about the deregulation of lipid composition in the pathogenesis of pulmonary fibrosis. The elongation of long-chain fatty acids family member 6 (Elovl6) is a rate-limiting enzyme catalysing the elongation of saturated and monounsaturated fatty acids. Here we show that Elovl6 expression is significantly downregulated after an intratracheal instillation of bleomycin (BLM) and in human lung with idiopathic pulmonary fibrosis. Elovl6-deficient (Elovl6⁻/⁻) mice treated with BLM exhibit severe fibroproliferative response and derangement of fatty acid profile compared with wild-type mice. Furthermore, Elovl6 knockdown induces a change in fatty acid composition similar to that in Elovl6⁻/⁻ mice, resulting in induction of apoptosis, TGF-β1 expression and reactive oxygen species generation. Our findings demonstrate a previously unappreciated role for Elovl6 in the regulation of lung homeostasis, and in pathogenesis and exacerbation of BLM-induced pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / deficiency
  • Acetyltransferases / genetics*
  • Animals
  • Apoptosis
  • Bleomycin
  • Drug Administration Routes
  • Fatty Acid Elongases
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Intubation, Intratracheal
  • Lipid Metabolism
  • Lung / metabolism*
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Reactive Oxygen Species / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism


  • ELOVL6 protein, human
  • Elovl6 protein, mouse
  • Fatty Acids
  • Reactive Oxygen Species
  • Transforming Growth Factor beta1
  • Bleomycin
  • Acetyltransferases
  • Fatty Acid Elongases