부산대학교 도서관

The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or chronic lipolysis associated with insulin resistance and/or insulin insufficiency disrupts metabolic homeostasis.sup.1,2. Coupled to lipolysis is the release of a recently identified hormone, fatty-acid-binding protein 4 (FABP4).sup.3. Although circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans.sup.4-7, no mechanism of action has yet been described.sup.8-10. Here we show that hormonal FABP4 forms a functional hormone complex with adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK) to regulate extracellular ATP and ADP levels. We identify a substantial effect of this hormone on beta cells and given the central role of beta-cell function in both the control of lipolysis and development of diabetes, postulate that hormonal FABP4 is a key regulator of an adipose-beta-cell endocrine axis. Antibody-mediated targeting of this hormone complex improves metabolic outcomes, enhances beta-cell function and preserves beta-cell integrity to prevent both type 1 and type 2 diabetes. Thus, the FABP4-ADK-NDPK complex, Fabkin, represents a previously unknown hormone and mechanism of action that integrates energy status with the function of metabolic organs, and represents a promising target against metabolic disease. Hormonal FABP4 is discovered to be a pivotal regulator of an adipose-beta-cell endocrine axis that coordinates energy status and metabolic organ function, and targeting this axis improved metabolic outcomes.
Author(s): Kacey J. Prentice [sup.1] , Jani Saksi [sup.1] , Lauren T. Robertson [sup.1] , Grace Y. Lee [sup.1] , Karen E. Inouye [sup.1] , Kosei Eguchi [sup.1] , Alexandra [...]