NAG-1/GDF15 transgenic mouse has less white adipose tissue and a reduced inflammatory response.
NAG-1/GDF15 transgenic mouse has less white adipose tissue and a reduced inflammatory response.
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DOI：
10.1155/2013/641851
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发表时间：
2013
影响因子：
4.6
通讯作者：
Eling TE
中科院分区：
文献类型：
--
作者：
Kim JM;Kosak JP;Kim JK;Kissling G;Germolec DR;Zeldin DC;Bradbury JA;Baek SJ;Eling TE
NAG-1/GDF15 是 TGF-β 超家族成员，其抑制炎症细胞因子产生的生物活性尚不明确。表达人 NAG-1/GDF15 (NAG-1Tg/Lox) 的转基因小鼠更瘦、体重更低，并且对化学或遗传诱导的肠道肿瘤具有抵抗力。由于肥胖、炎症和癌症之间的联系，我们检查了这些小鼠是否表现出对炎症刺激的反应减弱。根据细胞因子 KC、IL-6、MCP-1 和 TNFα 的血清水平，NAG-1Tg/Lox 小鼠对 LPS 的炎症反应降低。与文献报道和我们的体内结果相反，在体外RAW264.7细胞、小鼠腹腔巨噬细胞或小鼠肝库普弗细胞中，NAG-1不抑制LPS诱导的细胞因子表达，这表明NAG-1/GDF15不直接抑制LPS诱导的炎症细胞因子的产生。然而，NAG-1Tg/Lox 小鼠的白色脂肪组织较少，而白色脂肪组织是包括瘦素在内的炎症脂肪因子的主要来源。 NAG-1Tg/Lox 小鼠基础和 LPS 处理的血清瘦素和脂肪组织 mRNA 水平低于 WT 小鼠。我们认为，白色脂肪组织的减少和瘦素表达的减少可能部分是导致 NAG-1Tg/Lox 小鼠中观察到的 LPS 炎症反应减少和肠道肿瘤减少的原因。
NAG-1/GDF15 is a TGF-β superfamily member with poorly characterized biological activity proposed to inhibit inflammatory cytokine production. Transgenic mice expressing human NAG-1/GDF15 (NAG-1Tg/Lox) are leaner with lower body weight and are resistant to chemically or genetically induced intestinal tumors. Because of the link between obesity, inflammation, and cancer, we examined whether these mice exhibit a reduced response to inflammatory stimuli. The NAG-1Tg/Lox mice had a reduced inflammatory response to LPS based on the serum levels of cytokines KC, IL-6, MCP-1, and TNFα. In contrast to literature reports and our in vivo results, NAG-1 did not inhibit LPS-induced cytokine expression in vitro in RAW264.7 cells, mouse peritoneal macrophages, or mouse liver Kupffer cells, suggesting that NAG-1/GDF15 does not directly inhibit LPS-induced inflammatory cytokine production. However, NAG-1Tg/Lox mice have less white adipose tissue, the major source of inflammatory adipokines including leptin. Basal and LPS-treated serum leptin and mRNA levels in the adipose tissue of NAG-1Tg/Lox mice were lower than those in WT mice. We propose that the reduced white adipose tissue and reduced leptin expression may be responsible, in part, for the reduced inflammatory response to LPS and the decrease in intestinal tumors observed in NAG-1Tg/Lox mice.
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影响因子：
4.8
作者：
Jin, Young-June;Lee, Jeong-Hyung;Lee, Hansoo
通讯作者：
Lee, Hansoo
影响因子：
6.4
作者：
Teraoka, Naoya;Mutoh, Michihiro;Wakabayashi, Keiji
通讯作者：
Wakabayashi, Keiji
DOI：
10.1016/j.nut.2010.07.004
发表时间：
2011-03
期刊：
Nutrition (Burbank, Los Angeles County, Calif.)
影响因子：
--
作者：
Yarandi SS;Hebbar G;Sauer CG;Cole CR;Ziegler TR
通讯作者：
Ziegler TR
DOI：
10.1073/pnas.94.21.11514
发表时间：
1997-10-14
影响因子：
11.1
作者：
Bootcov, MR;Bauskin, AR;Breit, SN
通讯作者：
Breit, SN
影响因子：
29.4
作者：
Baek, Seung Joon;Okazaki, Ryuji;Eling, Thomas E.
通讯作者：
Eling, Thomas E.