Adhesion G‐protein coupled receptor 56 is required for 3T3‐L1 adipogenesis

Mohammad Al Hasan, Poornima Roy, Sharron Dolan, Patricia E. Martin, Steven Patterson, Chris Bartholomew*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
111 Downloads (Pure)


Obesity-associated conditions represent major global health and financial burdens and understanding processes regulating adipogenesis could lead to novel intervention strategies. This study shows that adhesion G-protein coupled receptor 56 (GPR56) gene transcripts are reduced in abdominal visceral white adipose tissue derived from obese Zucker rats versus lean controls. Immunostaining in 3T3-L1 preadipocytes reveals both mitotic cell restricted surface and low level general expression patterns of Gpr56. Gpr56 transcripts are differentially expressed in 3T3-L1 cells during adipogenesis. Transient knockdown (KD) of Gpr56 in 3T3-L1 cells dramatically inhibits differentiation through reducing the accumulation of both neutral cellular lipids (56%) and production of established adipogenesis Pparγ 2 (60–80%), C/ebpα (40–78%) mediator, and Ap2 (56–80%) marker proteins. Furthermore, genome editing of Gpr56 in 3T3-L1 cells created CW2.2.4 and RM4.2.5.5 clones (Gpr56 −/− cells) with compound heterozygous deletion frameshift mutations which abolish adipogenesis. Genome edited cells have sustained levels of the adipogenesis inhibitor β-catenin, reduced proliferation, reduced adhesion, altered profiles, and or abundance of extracellular matrix component gene transcripts for fibronectin, types I, III, and IV collagens and loss of actin stress fibers. β-catenin KD alone is insufficient to restore adipogenesis in Gpr56 −/− cells. Together these data show that Gpr56 is required for adipogenesis in 3T3-L1 cells. This report is the first demonstration that Gpr56 participates in regulation of the adipogenesis developmental program. Modulation of the levels of this protein and/or its biological activity may represent a novel target for development of therapeutic agents for the treatment of obesity.
Original languageEnglish
Pages (from-to)1601-1614
Number of pages14
JournalJournal of Cellular Physiology
Issue number2
Early online date15 Jul 2019
Publication statusPublished - Feb 2020


  • GPR56
  • adipogenesis
  • knockdown
  • genome editing
  • β‐catenin
  • extracellular matrix

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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