Antibody-mediated neutralization of ACBP/DBI has anorexigenic and lipolytic effects

• Published in: Adipocyte 2020-01, Vol.9 (1), p.116-119
• Main Authors: Sica, Valentina, Martins, Isabelle, Motiño, Omar, Bravo-San Pedro, José M., Kroemer, Guido
• Format: Article
• Language: English
• Subjects: Adiposity; Animals; anorexia; Anorexia - metabolism; Antibodies - metabolism; appetite; autophagy; Diazepam Binding Inhibitor - metabolism; Human health and pathology; Humans; Life Sciences; Lipolysis; Medicin och hälsovetenskap; obesity; Review
• ISSN: 2162-3945; 2162-397X; 2162-397X
• DOI: 10.1080/21623945.2020.1736734

We recently identified acyl coenzyme A-binding protein (ACBP)/diazepam binding inhibitor (DBI) as a novel 'hunger factor': a protein that is upregulated in human or murine obesity and that, if administered to mice, causes hyperphagy, adipogenesis and obesity. Conversely, neutralization of ACBP/DBI by systemic injection of neutralizing monoclonal antibodies or autoantibodies produced after auto-immunization against ACBP/DBI has anorexigenic and lipolytic effects. Thus, neutralization of ACBP/DBI results in reduced food intake subsequent to the activation of anorexigenic neurons and the inactivation of orexigenic neurons in the hypothalamus. Moreover, ACBP/DBI neutralization results into enhanced triglyceride lipolysis in white fat, a surge in free fatty acids in the plasma, enhanced incorporation of glycerol-derived carbon atoms into glucose, as well as an increase in β-oxidation, resulting in a net reduction of fat mass. Importantly, ACBP/DBI neutralization also stimulated an increase in autophagy in various organs, suggesting that it might mediate anti-ageing effects.