Eukaryotic cells release the phylogenetically ancient
protein acyl coenzyme A binding protein (ACBP, which in humans is encoded by the gene
DBI,
diazepam binding inhibitor) upon nutrient deprivation. Accordingly, mice that are starved for one to two days and humans that undergo voluntary fasting for one to three weeks manifest an increase in the plasma concentration of ACBP/
DBI. Paradoxically, ACBP/
DBI levels also increase in obese mice and humans. Since ACBP/
DBI stimulates appetite, this latter finding may explain why
obesity constitutes a self-perpetuating state. Here, we present a theoretical framework to embed these findings in the mechanisms of weight control, as well as a bioinformatics analysis showing that, irrespective of the human cell or tissue type, one single
isoform of ACBP/
DBI (ACBP1) is preponderant (~90% of all
DBI transcripts, with the sole exception of the testis, where it is ~70%). Based on our knowledge, we conclude that ACBP1 is subjected to a biphasic transcriptional and post-transcriptional regulation, explaining why
obesity and fasting both are associated with increased circulating ACBP1
protein levels.