title: Leucine-rich glioma inactivated 3 and tumor necrosis factor-α regulate mutually through NF-κB.
abstract: Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 increased in obese adipose tissues and suppressed adipogenesis through its receptor, ADAM23. We proposed that LGI3 may be a pro-inflammatory adipokine secreted predominantly by preadipocytes and macrophages. In this study, we showed that LGI3 and tumor necrosis factor-α (TNF-α) upregulated each other in 3T3-L1 cells. Treatment of 3T3-L1 preadipocytes with LGI3 protein increased TNF-α mRNA and protein. LGI3 treatment led to NF-κB activation and binding to an NF-κB binding site (-523 to -514) in TNF-α promoter. TNF-α treatment increased mRNA and protein expression of LGI3 and ADAM23. TNF-α increased NF-κB binding to a predicted binding site (-40 to -31) in LGI3 promoter. High fat diet-fed mice showed that LGI3 and TNF-α were increased and colocalized in adipose tissue inflammation. Taken together, these results suggested that mutual upregulation of LGI3 and TNF-α may play a role in adipose tissue inflammation in obesity.
authors: Department of Biochemistry, Chung-Ang University, College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul 156-861, Republic of Korea.
authors: Hyun A
authors: HA
authors: Kim
authors: Department of Biochemistry, Chung-Ang University, College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul 156-861, Republic of Korea.
authors: Nyoun Soo
authors: NS
authors: Kwon
authors: Department of Biochemistry, Chung-Ang University, College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul 156-861, Republic of Korea.
authors: Kwang Jin
authors: KJ
authors: Baek
authors: Department of Biochemistry, Chung-Ang University, College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul 156-861, Republic of Korea.
authors: Dong-Seok
authors: DS
authors: Kim
authors: Department of Biochemistry, Chung-Ang University, College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul 156-861, Republic of Korea. Electronic address: hyyunoffice@gmail.com.
authors: Hye-Young
authors: HY
authors: Yun
mesh_terms: D041721:3T3-L1 Cells; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D007249:Inflammation / Q000209:etiology; D007930:Leucine / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000209:etiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D054392:Adipokines; C511168:LGI3 protein, mouse; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D007930:Leucine
keywords: Adipokine; LGI3; NF-κB; Obesity; TNF-α