Cell-autonomous, paracrine and neuroendocrine feedback regulation of autophagy by DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein): the obesity factor.

Abstract

DBI/ACBP (diazepam binding protein, acyl-CoA binding protein) participates in the regulation of fatty acid metabolism when it is localized within cells, whereas outside of cells it acts as a diazepam-binding protein. Recent results indicate that many different mammalian cell types release DBI/ACBP upon in vitro or in vivo starvation in a macroautophagy/autophagy-dependent fashion. The autophagy-associated release of DBI/ACBP elicits feedback inhibition of autophagy through 3 independent mechanisms. First, the depletion of DBI/ACBP from cells limits autophagy in a cell-autonomous fashion. Second, extracellular DBI/ACBP acts in a paracrine fashion to inhibit autophagy. Third, DBI/ACBP increasing in the systemic circulation acts as an activator of lipo-anabolism and feeding behavior, thus removing the cause of autophagy induction (starvation) and suppressing the phenomenon. DBI/ACBP expression is upregulated at the mRNA and protein levels in obese mice and humans, and its extracellular neutralization by antibodies controls food intake and increases lipo-catabolism. Current data support the contention that DBI/ACBP is an important pro-obesity factor. Abbreviations: DBI: diazepam binding protein, acyl-CoA binding protein; GABR: gamma-aminobutyric acid type A receptor; TSPO: translocator protein.

• Authors: José Manuel Bravo-San Pedro, Valentina Sica, Isabelle Martins, Gerasimos Anagnostopoulos, Chiara Maiuri, Guido Kroemer
• Journal: Autophagy (Autophagy) Vol. 15 Issue 11 Pg. 2036-2038 (11 2019) ISSN: 1554-8635 [Electronic] United States
• PMID: 31470770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Comment)

Chemical References

• Diazepam Binding Inhibitor
• Receptors, GABA
• TSPO protein, human

Topics

• Animals
• Humans
• Mice
• Autophagy
• Diazepam Binding Inhibitor
• Obesity
• Receptors, GABA