Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity

ACBP is an appetite stimulator across phylogenetic barriers

“…Following the general rule that intracellular stress is communicated to the extracellular world [3], autophagy leads to the secretion of one particular phylogenetically ancient protein, which is acyl coenzyme A-binding protein (ACBP, also called diazepam-binding inhibitor, DBI) into the extracellular space. This phenomenon has been first documented for unicellular fungi and optionally multicellular slime molds [4], and has later been confirmed for mammalian cells [5].…”

“…Dietary interventions causing weight loss cause a transient reduction in ACBP/DBI mRNA expression in the periumbilical fat, while successful bariatric surgery results in reduced ACBP/DBI plasma levels. This suggest a role for ACBP/DBI in the pathogenesis of obesity as well [5].…”

“…That said, there are species specificities, because ACBP/DBI acts on a metabotropic receptor (Ste3) in yeast, but on ionotropic gamma-aminobytyric (GABA) A receptors in mice [7], suggesting that the effector of ACBP/DBI have changed during evolution. Moreover, in yeast it appears that the genetic removal of ACBP/DBI inhibits autophagy, contrasting with findings in C. elegans, mice and human cell cultures in which removal ACBP/DBI stimulates autophagy [5,7]. Whether autophagy modulation is involved in appetite control has not yet been elucidated.…”

“…As an intracellular protein, it binds acyl coenzyme-A molecules, facilitating their intracellular trafficking. As an extracellular protein, it binds to cell surface receptors to stimulate signals that affect the behavior of cells and organisms in an autocrine, paracrine and endocrine fashion [5,6].…”

“…Administration of the recombinant ACBP/DBI protein or its transgenic overexpression in liver cells, causing an increase in ACBP/DBI plasma levels, leads to hyperphagy and triggers lipo-anabolic reactions favoring adiposity, obesity and fatty liver. In sharp contrast, neutralization of ACBP/DBI by injection of antibodies reduces food intake and favors lipocatabolic reactions including triglyceride lipolysis and fatty acid oxidation, thus reducing fat mass [5,9]. Mice that are rendered obese by a high-fat diet or that become spontaneously obese (on a normal diet) due to a genetic leptin deficiency exhibit elevated ACBP/DBI RNA and protein levels in their tissues, as well as increased ACBP/DBI protein in their blood [5,9].…”