Kim Hyun A, Baek Kwang Jin, Yun Hye-Young
Department of Biochemistry, Chung-Ang University, College of Medicine, Seoul 06974, Republic of Korea.
Exp Ther Med. 2021 Aug;22(2):837. doi: 10.3892/etm.2021.10269. Epub 2021 Jun 4.
LGI family member 3 (LGI3) is a member of the LGI protein family. In our previous studies, LGI3 was determined to be expressed in adipose tissues, skin and the brain, where it served as a pleiotropic cytokine. The results indicated that LGI3 levels are increased in adipose tissues of obese individuals in comparison with control individuals and that LGI3 suppressed adipogenesis via its receptor, disintegrin and metalloproteinase domain-containing protein 23. Additionally, it was reported that LGI3 upregulates tumor necrosis factor-α and downregulated adiponectin and hypothesized that LGI3 may act as a proinflammatory adipokine involved in adipose tissue inflammation. In the present study, cytokine arrays were used to analyze cytokine levels in adipose tissues and plasma of LGI3-knockout mice and signaling protein arrays used to analyze the expression and phosphorylation of these proteins in LGI3-treated preadipocytes. The results suggested that expression levels of 129 gene products (24 cytokines and 105 signaling proteins) were altered in response to LGI3 deficiency or LGI3 treatment, respectively. Protein-protein interaction network analysis of LGI3-regulated gene products revealed that 94% of the gene products (21 cytokines and 100 signaling proteins) formed an interaction network cluster. Functional enrichment analysis for the LGI3-regulated gene products, including those from our previous studies, revealed an association with numerous biological processes, including inflammatory responses, cellular differentiation and development and metabolic regulation. Gene co-expression network analysis revealed that these LGI3-regulated gene products were involved in various biological processes in an overlapping and differential manner between subcutaneous and visceral adipose tissues. Notably, inflammatory responses were more strongly associated with the LGI3-regulated gene co-expression network in visceral adipose tissues than in subcutaneous adipose tissues. Analysis of expression quantitative trait loci identified four single nucleotide variants that affect expression of LGI3 in an adipose depot-specific manner. Taken together, the results suggested that LGI3 may serve depot-specific roles as an adipokine in adipose tissues.
富含亮氨酸重复序列免疫球蛋白样蛋白3（LGI3）是LGI蛋白家族的成员。在我们之前的研究中，LGI3被确定在脂肪组织、皮肤和大脑中表达，在这些组织中它作为一种多效性细胞因子发挥作用。结果表明，与对照个体相比，肥胖个体脂肪组织中LGI3水平升高，并且LGI3通过其受体——含去整合素和金属蛋白酶结构域蛋白23抑制脂肪生成。此外，据报道LGI3上调肿瘤坏死因子-α并下调脂联素，并推测LGI3可能作为一种促炎脂肪因子参与脂肪组织炎症。在本研究中，使用细胞因子阵列分析LGI3基因敲除小鼠脂肪组织和血浆中的细胞因子水平，并使用信号蛋白阵列分析LGI3处理的前脂肪细胞中这些蛋白的表达和磷酸化。结果表明，分别有129种基因产物（24种细胞因子和105种信号蛋白）的表达水平因LGI3缺乏或LGI3处理而发生改变。对LGI3调节的基因产物进行蛋白质-蛋白质相互作用网络分析发现，94%的基因产物（21种细胞因子和100种信号蛋白）形成一个相互作用网络簇。对LGI3调节的基因产物进行功能富集分析，包括我们之前研究中的那些产物，发现其与众多生物学过程相关，包括炎症反应、细胞分化和发育以及代谢调节。基因共表达网络分析表明，这些LGI3调节的基因产物以重叠和差异的方式参与皮下和内脏脂肪组织中的各种生物学过程。值得注意的是，与皮下脂肪组织相比，炎症反应与内脏脂肪组织中LGI3调节的基因共表达网络的关联更强。表达数量性状位点分析确定了四个单核苷酸变体，它们以脂肪库特异性方式影响LGI3的表达。综上所述，结果表明LGI3可能作为一种脂肪因子在脂肪组织中发挥脂肪库特异性作用。
