Molecular mechanisms of FOXO1 in adipocyte differentiation

J Mol Endocrinol. 2019 Apr 1;62(3):R239-R253. doi: 10.1530/JME-18-0178.

Abstract

Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.

Keywords: 14-3-3; FOXO1; adipocyte differentiation; microRNA; obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Animals
  • Cell Differentiation / physiology
  • Forkhead Box Protein O1 / metabolism*
  • Humans
  • MicroRNAs / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • Signal Transduction / physiology

Substances

  • 14-3-3 Proteins
  • Forkhead Box Protein O1
  • MicroRNAs