FABP4

Uncontrolled or chronic lipolysis, often associated with insulin resistance and/or insulin insufficiency, disrupts metabolic homeostasis. A newly identified hormone, fatty-acid-binding protein 4 (FABP4), is released during lipolysis and has been strongly linked to cardiometabolic diseases. However, its mechanism of action remains unclear. In this study, we demonstrate that FABP4 forms a functional complex with adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK), which regulates extracellular ATP and ADP levels. This hormone complex, which we term Fabkin, has a significant effect on beta-cell function, a central regulator of both lipolysis and diabetes development. We propose that FABP4 is a key component of an adipose-beta-cell endocrine axis. Targeting this hormone complex with antibodies improves metabolic outcomes, enhances beta-cell function, and preserves beta-cell integrity, thereby preventing both type 1 and type 2 diabetes. Our findings introduce the FABP4-ADK-NDPK complex as a novel hormone and mechanism that integrates energy status with metabolic organ function, highlighting it as a promising therapeutic target for metabolic diseases.