A hormone complex of FABP4 and nucleoside kinases regulates islet function
| Autor: | Kacey J. Prentice, Jani Saksi, Lauren T. Robertson, Grace Y. Lee, Karen E. Inouye, Kosei Eguchi, Alexandra Lee, Ozgur Cakici, Emily Otterbeck, Paulina Cedillo, Peter Achenbach, Anette-Gabriele Ziegler, Ediz S. Calay, Feyza Engin, Gökhan S. Hotamisligil |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Nature 600, 720–726 (2021) Nature |
| Popis: | 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(1,2). Coupled to lipolysis is the release of a recently identified hormone, fatty acid-binding protein 4 (FABP4)(3). While circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans(4–7), no mechanism of action has yet been described(8–10). Here, we show that hormonal FABP4 forms a novel functional hormone complex with Adenosine Kinase (ADK) and Nucleoside Diphosphate Kinase (NDPK) to regulate extracellular ATP and ADP levels. We identify a substantial impact 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, Fabtin, represents a previously unknown hormone and mechanism of action integrating energy status with the function of metabolic organs, representing a promising target against metabolic disease. |
| Databáze: | OpenAIRE |
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