Figure 3. Pleiotropic roles of ACBP/DBI as a secreted extracellular (in blue) and intracellular (in red) protein on peripheral lipid metabolism, hormone secretion and brain functions.

In most cells, intracellular ACBP plays a key role in intracellular fatty acid fluxes and metabolism including LCFACoA oxidation and esterification in neural and tumor cells as well as lipogenesis in fat and liver cells. In the skin, ACBP promotes ceramide and very-long chain fatty acid synthesis which is essential to maintain the trans-epidermal barrier and energy homeostasis. In the brain, secreted ACBP promotes neurogenesis and neuroprotection via GABA_AR and ODN-GPCR-dependent pathways respectively. In addition, extracellular ACBP modulates synaptic transmission, neural function, and diverse types of behavior including feeding behavior. Circulating ACBP levels are affected by changes in the metabolic status and fat mass. Extracellular ACBP regulates hormone secretion in the gut (CCK) and endocrine pancreas (insulin) as well as lipid metabolism in adipocytes. Peripheral administration of ACBP promotes feeding and anabolic pathways (lipogenesis in liver and fat cells) though it remains unclear whether the effects of exogenous ACBP on metabolism and food intake are direct (via GABA_AR and/or ODN-GPCR) and/or indirect (via hormone secretion and/or afferent neurons).