Unconventional secretion of FABP4 by endosomes and secretory lysosomes

J Cell Biol. 2018 Feb 5;217(2):649-665. doi: 10.1083/jcb.201705047. Epub 2017 Dec 6.


An appreciation of the functional properties of the cytoplasmic fatty acid binding protein 4 (FABP4) has advanced with the recent demonstration that an extracellular form secreted by adipocytes regulates a wide range of physiological functions. Little, however, is known about the mechanisms that mediate the unconventional secretion of FABP4. Here, we demonstrate that FABP4 secretion is mediated by a membrane-bounded compartment, independent of the conventional endoplasmic reticulum-Golgi secretory pathway. We show that FABP4 secretion is also independent of GRASP proteins, autophagy, and multivesicular bodies but involves enclosure within endosomes and secretory lysosomes. We highlight the physiological significance of this pathway with the demonstration that an increase in plasma levels of FABP4 is inhibited by chloroquine treatment of mice. These findings chart the pathway of FABP4 secretion and provide a potential therapeutic means to control metabolic disorders associated with its dysregulated secretion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Cells, Cultured
  • Endosomes / metabolism*
  • Fatty Acid-Binding Proteins / metabolism*
  • Lysosomes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Secretory Pathway


  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins