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Abstract
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.
Highlights
Acyl coenzyme A binding protein (ACBP), which in humans is encoded by the gene diazepam binding inhibitor (DBI), is a phylogenetically ancient protein that is ubiquitously expressed by all nucleated human cell types [1,2,3]
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
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
Summary
Acyl coenzyme A binding protein (ACBP), which in humans is encoded by the gene DBI (diazepam binding inhibitor), is a phylogenetically ancient protein that is ubiquitously expressed by all nucleated human cell types [1,2,3]. The transcript encoding the ACBP1 isoform was uniformly expressed at high levels (with the sole exception of whole blood cells), in accord with the observation that the ACBP protein (detected by immunohistochemistry) is present in all human tissues [9]. A similar autophagy-dependent release mechanism for ACBP/DBI was documented for primary human or mouse cells, including circulating leukocytes and hepatocytes cultured under nutrient-free conditions, knowing that nutrient deprivation is one of the most important physiological stimuli of autophagy [7] This starvation-dependent release of ACBP/DBI concerns a preexisting pool of the protein and is not coupled to an increased transcription of the ACBP/DBI gene [7]. The levels of mRNA coding for ACBP/DBI tended to decrease upon starvation in the liver and white adipose tissue from mice [7] These results suggest that the starvation-induced redistribution of pre-synthesized ACBP/DBI protein depends on autophagy.
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