Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes

Int J Obes (Lond). 2014 Sep;38(9):1221-7. doi: 10.1038/ijo.2013.241. Epub 2013 Dec 19.


Background: Fatty acid binding protein 4 (FABP4) is a predominantly cytosolic protein of the adipocytes, but also abundantly present in human plasma; its plasma concentrations were linked to obesity and metabolic syndrome. Recent studies have suggested a direct extracellular effect of FABP4 in the regulation of glucose metabolism and heart function independently of its effect as a carrier protein. Interestingly, FABP4 has no secretory signal sequence; hence, the mechanisms how FABP4 is released from adipocytes are unclear.

Methods and results: In this study we investigated the mechanisms for FABP4 secretion from human adipocytes by using isolated primary pre-adipocytes (PAs) and the human adipocyte cell strain Simpson-Golabi-Behmel syndrome. In undifferentiated PAs, FABP4 expression was barely detectable and increased continuously during differentiation. The increase in FABP4 mRNA expression was accompanied by high levels of FABP4 secretion. In differentiated human adipocytes, FABP4 secretion was not abolished by blocking the Golgi-dependent secretory pathway in vitro, supporting a non-classical secretion mechanism for FABP4. However, raising intracellular Ca(2+) levels enhanced FABP4 secretion in a concentration-dependent manner.

Conclusion: This study shows that FABP4 is actively released from human adipocytes in vitro via a non-classical, calcium-dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology
  • Calcium / metabolism*
  • Calcium Signaling
  • Cell Differentiation
  • Cells, Cultured
  • Fatty Acid-Binding Proteins / metabolism*
  • Genetic Diseases, X-Linked / metabolism*
  • Genetic Diseases, X-Linked / physiopathology
  • Gigantism / metabolism*
  • Gigantism / physiopathology
  • Heart Defects, Congenital / metabolism*
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Intellectual Disability / metabolism*
  • Intellectual Disability / physiopathology
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / physiopathology
  • Obesity / metabolism*
  • Obesity / physiopathology
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction


  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • RNA, Messenger
  • Calcium

Supplementary concepts

  • Simpson-Golabi-Behmel syndrome