PMID- 31304602 OWN - NLM STAT- MEDLINE DCOM- 20201016 LR - 20201016 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 235 IP - 2 DP - 2020 Feb TI - Adhesion G-protein coupled receptor 56 is required for 3T3-L1 adipogenesis. PG - 1601-1614 LID - 10.1002/jcp.29079 [doi] AB - 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 Ppargamma (2) (60-80%), C/ebpalpha (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 beta-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. beta-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. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Al Hasan, Mohammad AU - Al Hasan M AD - Department of Biological & Biomedical Sciences, School of Health & Life Sciences, Glasgow Caledonian University, Glasgow, Scotland. FAU - Roy, Poornima AU - Roy P AD - Department of Biological & Biomedical Sciences, School of Health & Life Sciences, Glasgow Caledonian University, Glasgow, Scotland. FAU - Dolan, Sharron AU - Dolan S AD - Department of Biological & Biomedical Sciences, School of Health & Life Sciences, Glasgow Caledonian University, Glasgow, Scotland. FAU - Martin, Patricia E AU - Martin PE AUID- ORCID: 0000-0003-0890-8059 AD - Department of Biological & Biomedical Sciences, School of Health & Life Sciences, Glasgow Caledonian University, Glasgow, Scotland. FAU - Patterson, Steven AU - Patterson S AD - Department of Biological & Biomedical Sciences, School of Health & Life Sciences, Glasgow Caledonian University, Glasgow, Scotland. FAU - Bartholomew, Chris AU - Bartholomew C AUID- ORCID: 0000-0002-1153-8389 AD - Department of Biological & Biomedical Sciences, School of Health & Life Sciences, Glasgow Caledonian University, Glasgow, Scotland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190715 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Adgrg1 protein, rat) RN - 0 (GPR56 protein, mouse) RN - 0 (Receptors, G-Protein-Coupled) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*metabolism MH - Adipogenesis/*physiology MH - Animals MH - Gene Knockdown Techniques MH - Male MH - Mice MH - Obesity/metabolism MH - Rats MH - Rats, Zucker MH - Receptors, G-Protein-Coupled/*metabolism OTO - NOTNLM OT - GPR56 OT - adipogenesis OT - extracellular matrix OT - genome editing OT - knockdown OT - beta-catenin EDAT- 2019/07/16 06:00 MHDA- 2020/10/21 06:00 CRDT- 2019/07/16 06:00 PHST- 2019/04/09 00:00 [received] PHST- 2019/06/14 00:00 [accepted] PHST- 2019/07/16 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2019/07/16 06:00 [entrez] AID - 10.1002/jcp.29079 [doi] PST - ppublish SO - J Cell Physiol. 2020 Feb;235(2):1601-1614. doi: 10.1002/jcp.29079. Epub 2019 Jul 15.