Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects

Authors:

Sijing Li1-3,#, Adrien Joseph1-3,#, Isabelle Martins1,2 and Guido Kroemer1,2,4-6
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Affiliations:

1 Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université de Paris, Sorbonne Université, Paris, France.

2 Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.

3 Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, France.

4 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.

5 Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.

6 Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden.

# SL and AJ equally contributed to this paper.

Keywords: 

metabolism, obesity, diazepam binding protein, appetite, starvation, autophagy.

Abbreviations:

ACBP – acyl coenzyme A binding protein,

DBI – diazepam binding inhibitor,

GABAAR – γ-aminobutyric acid A receptor.

Corresponding Author(s):

Guido Kroemer, Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Phone: +33 1 44 27 76 67; Fax: +33 1 44 27 76 74; kroemer@orange.fr Isabelle Martins, Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Phone: +33 1 44 27 76 62; Fax: +33 1 44 27 76 74; isabelle.martins@inserm.fr

Conflict of interest statement:

G.K. has filed patent application dealing with targeting the ACBP/DBI system in anorexia, obesity, and co-morbidities, as well as patent applications dealing with caloric restriction mimetics (autophagy inducers) for the treatment of aging, age-related diseases, cancer, obesity, and co-morbidities. G.K. is a scientific co-founder of everImmune, Samsara Therapeutics and Therafast Bio.

Please cite this article as:

Sijing Li, Adrien Joseph, Isabelle Martins and Guido Kroemer (2021). Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects. Cell Stress 5(7): 89-98. doi: 10.15698/cst2021.07.252

© 2021 Li et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

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.