ACBP/DBI protein neutralization confers autophagy-dependent organ protection through inhibition of cell loss, inflammation, and fibrosis

Proc Natl Acad Sci U S A. 2022 Oct 11;119(41):e2207344119. doi: 10.1073/pnas.2207344119. Epub 2022 Oct 3.


Acyl-coenzyme A (CoA)-binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular feedback regulator of autophagy. Here, we report that injection of a monoclonal antibody neutralizing ACBP/DBI (α-DBI) protects the murine liver against ischemia/reperfusion damage, intoxication by acetaminophen and concanavalin A, and nonalcoholic steatohepatitis caused by methionine/choline-deficient diet as well as against liver fibrosis induced by bile duct ligation or carbon tetrachloride. α-DBI downregulated proinflammatory and profibrotic genes and upregulated antioxidant defenses and fatty acid oxidation in the liver. The hepatoprotective effects of α-DBI were mimicked by the induction of ACBP/DBI-specific autoantibodies, an inducible Acbp/Dbi knockout or a constitutive Gabrg2F77I mutation that abolishes ACBP/DBI binding to the GABAA receptor. Liver-protective α-DBI effects were lost when autophagy was pharmacologically blocked or genetically inhibited by knockout of Atg4b. Of note, α-DBI also reduced myocardium infarction and lung fibrosis, supporting the contention that it mediates broad organ-protective effects against multiple insults.

Keywords: acyl-CoA binding protein; autophagy; fibrosis; myocardium infarction; non-alcoholic steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antioxidants
  • Autoantibodies / metabolism
  • Autophagy
  • Carbon Tetrachloride
  • Carrier Proteins / genetics
  • Choline
  • Coenzyme A / metabolism
  • Concanavalin A / metabolism
  • Diazepam
  • Diazepam Binding Inhibitor* / metabolism
  • Fatty Acids / metabolism
  • Fibrosis
  • Inflammation
  • Methionine
  • Mice
  • Receptors, GABA-A*


  • Acetaminophen
  • Antibodies, Monoclonal
  • Antioxidants
  • Autoantibodies
  • Carbon Tetrachloride
  • Carrier Proteins
  • Choline
  • Coenzyme A
  • Concanavalin A
  • Diazepam
  • Diazepam Binding Inhibitor
  • Fatty Acids
  • Methionine
  • Receptors, GABA-A