ESPEYB19 15. Editors’ Choice New Hormones (2 abstracts)
15.6. A hormone complex of FABP4 and nucleoside kinases regulates islet function
Prentice KJ , Saksi J , Robertson LT , Lee GY , Inouye KE , Eguchi K , Lee A , Cakici O , Otterbeck E , Cedillo P , Achenbach P , Ziegler AG , Calay ES , Engin F & Hotamisligil GS
Nature. 2021;600(7890):720-6. doi: 10.1038/s41586-021-04137-3.PubMed ID: 34880500
Brief summary: This mouse study identifies FABP4 (‘Fabkin’) as a new fat-derived hormone that regulates insulin-producing beta cells in the pancreas.
We have learnt over the recent years that body fat is not simply a passive energy storage tissue, but instead secretes a number of active peptides that influence appetite regulation, insulin sensitivity and inflammatory pathways. These authors now identify a new adipocyte-derived hormone, which they call ‘Fabkin’, which is released on lipolysis and acts to stimulate pancreatic islet cell function.
There are several unique characteristics of this new hormone. The authors claim that Fabkin is the only known hormone that is released from adipose tissue by lipolysis. Unlike traditional hormones which typically comprise a single molecule and act on a single receptor, Fabkin comprises a functional multi-protein complex, including fatty acid binding protein 4 (FABP4), adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK). Furthermore, it establishes a novel adipocyte-beta cell endocrine axis.
In humans, FABP4 is increased in type 2 diabetes (T2D) and correlates with body–mass index (BMI), and the authors also showed that circulating FABP4 is ~1.6-fold higher in patients with new-onset T1D compared with non-diabetic individuals. In mice, blocking Fabkin using antibody-mediated targeting of the hormone complex improved metabolic outcomes, enhanced beta-cell function and preserved beta-cell integrity in mouse models of type 1 and type 2 diabetes. Beyond the beta cell, Fabkin showed a diverse activity profile, including on inflammation, insulin resistance and cardiac pathophysiology. Is this too good to be true, or will Fabkin be a future therapeutic target for obesity-related metabolic diseases?
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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