Rutin suppresses palmitic acids-triggered inflammation in macrophages and blocks high fat diet-induced obesity and fatty liver in mice.
Rutin suppresses palmitic acids-triggered inflammation in macrophages and blocks high fat diet-induced obesity and fatty liver in mice.
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DOI：
10.1007/s11095-013-1125-1
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发表时间：
2013-11
影响因子：
3.7
通讯作者：
Liu, Dexi
中科院分区：
文献类型：
--
作者：
Gao, Mingming;Ma, Yongjie;Liu, Dexi
阐明芦丁阻断巨噬细胞介导的炎症和高脂饮食引起的肥胖和脂肪肝的机制。采用体外和体内方法评估芦丁对培养巨噬细胞中棕榈酸引发的炎症的影响，以及对高脂肪饮食小鼠体重增加和脂肪肝发展的影响。棕榈酸可增加促炎细胞因子的 mRNA 水平，并提高培养的巨噬细胞中 TNFα 的产生。预先将芦丁暴露于细胞可以极大地抑制这些升高。芦丁抑制的炎症与负责内质网应激和活性氧产生的基因转录减少相关。在体内，芦丁可以保护小鼠免受高脂肪饮食引起的肥胖、脂肪肝和胰岛素抵抗。保护作用与白色脂肪组织中缺乏肥大和冠状结构、降低巨噬细胞标记基因（包括 F4/80、Cd11c 和 Cd68）的 mRNA 水平以及抑制白色脂肪组织中参与慢性炎症的基因（如 Mcp1 和 Tnfα）的转录有关。此外，芦丁还能增加棕色脂肪组织中负责能量消耗的基因的表达，包括 Pgc1α 和 Dio2。此外，芦丁还能抑制肝脏中 Srebp1c 和 Cd36 的转录，从而阻止脂肪肝的发展。这些结果表明，补充芦丁是阻断巨噬细胞介导的炎症和炎症诱导的肥胖及其相关并发症的有前途的策略。
To elucidate the mechanism of rutin in blocking macrophage-mediated inflammation and high fat diet-induced obesity and fatty liver. Both in vitro and in vivo approaches were taken in evaluating the effects of rutin on palmitic acids-triggered inflammation in cultured macrophages, and on weight gain and development of fatty liver of mice fed a high fat diet. Palmitic acids increase mRNA levels of pro-inflammatory cytokines, and elevate the production of TNFα in cultured macrophages. Pre-exposure of rutin to cells greatly suppressed these elevations. The suppressed inflammation by rutin was correlated with a decrease in transcription of genes responsible for ER stress and production of reactive oxygen species. In vivo, rutin protects mice from high fat diet-induced obesity, fatty liver and insulin resistance. The protective effects were associated with lack of hypertrophy and crown-like structures in the white adipose tissue, decreased mRNA levels of marker genes for macrophages including F4/80, Cd11c and Cd68, and repressed transcription of genes involved in chronic inflammation such as Mcp1 and Tnfα in white adipose tissue. In addition, rutin increases the expression of genes responsible for energy expenditure in brown adipose tissue including Pgc1α and Dio2. Furthermore, rutin suppresses transcription of Srebp1c and Cd36 in the liver, leading to a blockade of fatty liver development. These results suggest that supplementation of rutin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.
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DOI：
10.1084/jem.20102049
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bulua AC;Simon A;Maddipati R;Pelletier M;Park H;Kim KY;Sack MN;Kastner DL;Siegel RM
通讯作者：
Siegel RM
DOI：
10.1073/pnas.1011736107
发表时间：
2010-10-12
影响因子：
11.1
作者：
Goodall, Jane C.;Wu, Changxin;Gaston, J. S. Hill
通讯作者：
Gaston, J. S. Hill
影响因子：
3.3
作者：
Kamalakkannan, N.;Prince, P. Stanely Mainzen
通讯作者：
Prince, P. Stanely Mainzen
影响因子：
4.2
作者：
Panchal, Sunil K.;Poudyal, Hemant;Brown, Lindsay
通讯作者：
Brown, Lindsay
影响因子：
168.9
作者：
Samuel, Varman T.;Petersen, Kitt Falk;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.