Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity

Lindsay E. Wu, Dorit Samocha-Bonet, P. Tess Whitworth, Daniel J. Fazakerley, Nigel Turner, Trevor J. Biden, David E. James, James Cantley

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46 Citations (Scopus)

Abstract

A critical feature of obesity is enhanced insulin secretion from pancreatic β-cells, enabling the majority of individuals to maintain glycaemic control despite adiposity and insulin resistance. Surprisingly, the factors coordinating this adaptive β-cell response with adiposity have not been delineated. Here we show that fatty acid binding protein 4 (FABP4/aP2) is an adipokine released from adipocytes under obesogenic conditions, such as hypoxia, to augment insulin secretion. The insulinotropic action of FABP4 was identified using an invitro system that recapitulates adipocyte to β-cell endocrine signalling, with glucose-stimulated insulin secretion (GSIS) as a functional readout, coupled with quantitative proteomics. Exogenous FABP4 potentiated GSIS invitro and invivo, and circulating FABP4 levels correlated with GSIS in humans. Insulin inhibited FABP4 release from adipocytes invitro, in mice and in humans, consistent with feedback regulation. These data suggest that FABP4 and insulin form an endocrine loop coordinating the β-cell response to obesity.

Original languageEnglish
Pages (from-to)465-473
Number of pages9
JournalMolecular Metabolism
Volume3
Issue number4
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Adipocyte
  • Adipokine
  • Beta-cell
  • FABP4
  • Insulin secretion
  • Obesity

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    Wu, L. E., Samocha-Bonet, D., Whitworth, P. T., Fazakerley, D. J., Turner, N., Biden, T. J., James, D. E., & Cantley, J. (2014). Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity. Molecular Metabolism, 3(4), 465-473. https://doi.org/10.1016/j.molmet.2014.02.005