Acyl-CoA-binding protein (ACBP): the elusive ‘hunger factor’ linking autophagy to food intake
Authors:José Manuel Bravo-San Pedro1-3, Valentina Sica1-3, Frank Madeo4,5 and Guido Kroemer1-3,6-8
1 INSERM U1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, 15 rue de l’école de médecine 75006, Paris, France.
2 Team “Metabolism, Cancer & Immunity” labellisée par la Ligue contre le Cancer, Paris, France.
3 Cell Biology and Metabolomics platforms, Gustave Roussy Cancer Campus, Villejuif, France.
4 Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, 8010, Austria.
5 BioTechMed Graz, Graz, 8010, Austria.
6 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
7 Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China.
8 Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden.
Keywords:
appetite control, diazepam binding protein, metabolism, obesity, unconventional protein secretion.
Abbreviatons:
ACBP - Acyl-CoA-binding protein,
AcCoA – acetyl coenzyme A,
CRM - caloric restriction mimetic,
DBI - diazepam-binding protein.
Corresponding Author(s):
Conflict of interest statement:
J.M.B.-S.P. and G.K. filed a patent application dealing with targeting the ACBP/DBI system in anorexia, obesity, and co-morbidities. G.K. filed additional patent applications dealing with caloric restriction mimetics (autophagy in-ducers) for the treatment of aging, age-related diseases, cancer, obesity, and co-morbidities. G.K. is a scientific co-founder of Samsara Therapeutics and Therafast Bio.
Please cite this article as:
José Manuel Bravo-San Pedro, Valentina Sica, Frank Madeo and Guido Kroemer (2019). Acyl-CoA-binding protein (ACBP): the elusive ‘hunger factor’ linking autophagy to food intake. Cell Stress 3(10): 312-318. doi: 10.15698/cst2019.10.200
© 2019 Bravo-San Pedro 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 re-production in any medium, provided the original author and source are acknowledged.
Abstract:
The best-known appetite-regulating factors identified in rodents are leptin, an appetite inhibitor, and ghrelin, an appetite stimulator. Rare cases of loss-of-functions mutations affecting leptin and its receptor, as well as polymorphisms concerning ghrelin and its receptor, have been documented in human obesity, apparently validating the relevance of leptin and ghrelin for human physiology. Paradoxically, however, the overwhelming majority of obese individuals manifest high leptin and low ghrelin plasma levels, suggesting that both factors are not directly disease-relevant. We recently discovered that acyl-CoA-binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), acts as an efficient lipogenic and appetite stimulator in mice. Indeed, in response to starvation, ACBP/DBI is released from tissues in an autophagy-dependent fashion and increases in the plasma. Intravenous injection of ACBP/DBI stimulates feeding behavior through a reduction of circulating glucose levels, and consequent activation of orexigenic neurons in the hypothalamus. In contrast, neutralization of ACBP/DBI abolishes the hyperphagia observed after starvation of mice. Of note, ACBP/DBI is increased in the plasma of obese persons and mice, pointing to a convergence (rather than divergence) between its role in appetite stimulation and human obesity. Based on our results, we postulate a novel ‘hunger reflex’ in which starvation induces a surge in extracellular ACBP/DBI, which in turn stimulates feeding behavior. Thus, ACBP/DBI might be the elusive ‘hunger factor’ that explains increased food uptake in obesity.