title: Leucine-rich glioma inactivated 3 regulates adipogenesis through ADAM23.
abstract: Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein and a member of LGI/epitempin family. We previously showed that LGI3 was highly expressed in brain and played regulatory roles in neuronal exocytosis and differentiation. Besides the nervous system, LGI3 was shown to be expressed in diverse tissues. In this study, we found that LGI3 and its receptor candidate ADAM23 were expressed in adipose tissues and 3T3-L1 cells. 3T3-L1 preadipocytes secreted a 60-kDa protein, a major secreted form of LGI3, which declined with adipocyte differentiation. LGI3 was also expressed in adipose tissue macrophages in the ob/ob mice and in macrophage cell line. The 60-kDa LGI3 protein was selectively increased in the ob/ob adipose tissues comparing with the lean mice. Pull-down experiments, coimmunoprecipitation and immunocytochemistry indicated that LGI3 associated with ADAM23 in adipose tissues and 3T3-L1 cells. Knockdown of LGI3 or ADAM23 by siRNA increased adipogenesis in 3T3-L1 cells. Treatment with LGI3 protein did not affect preadipocyte proliferation but attenuated adipogenesis and this effect was reversed by siRNA-mediated knockdown of ADAM23. Taken together, we propose that LGI3 may be a candidate adipokine that is perturbed in obesity and suppresses adipogenesis through its receptor, ADAM23.
authors.affiliation: Department of Biochemistry, Chung-Ang University, College of Medicine, 84 Heukseok-ro, Seoul 156-861, Republic of Korea.
authors.forename: Hyun A
authors.initials: HA
authors.lastname: Kim
authors.forename: Woo-Jae
authors.initials: WJ
authors.lastname: Park
authors.forename: Hyo-Soon
authors.initials: HS
authors.lastname: Jeong
authors.forename: Hyun-e
authors.initials: HE
authors.lastname: Lee
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Yun
mesh_terms: D041721:3T3-L1 Cells; D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C511168:LGI3 protein, mouse; D009419:Nerve Tissue Proteins; D051722:ADAM Proteins; C121259:Adam23 protein, mouse