Dbi, also known as Diazepam Binding Inhibitor or Acyl-CoA Binding Protein (ACBP), is a phylogenetically conserved paracrine inhibitor of macroautophagy/autophagy [1]. It acts as a pro-aging molecule and is involved in lipid metabolism regulation [1,5]. Depending on its levels and sub-cellular localization, it can modulate lipid anabolism or catabolism, and it is secreted by an autophagy-dependent mechanism [5]. Genetic loss-of-function models have been crucial in understanding its physiological roles in vivo [4].

In KO mouse models, knockout of Acb1 (yeast equivalent of human Dbi/ACBP) induces autophagy and prolongs lifespan in an autophagy-dependent manner, indicating its role as a pro-aging factor [1]. In adipose tissue, knockout of Acbp/Dbi prevents high-fat diet-induced weight gain in mice, suggesting its importance in body mass homeostasis [6]. Antibody-mediated neutralization of Dbi/ACBP in mice reduces signs of anthracycline-accelerated cardiac aging, such as the up-regulation of the senescence marker CDKN2A/p16 and functional decline of the heart [1]. It also has anorexigenic and lipolytic effects, and can protect murine organs like the liver against various damages, including ischemia/reperfusion, intoxication, and fibrosis [2,3].

In conclusion, Dbi plays essential roles in autophagy regulation, aging, lipid metabolism, and body mass homeostasis. Gene knockout mouse models have significantly contributed to understanding its functions in age-associated cardiovascular diseases, obesity-related metabolic disorders, and organ-protective mechanisms, providing potential therapeutic targets for these diseases.