The antioxidant tempol transforms gut microbiome to resist obesity in female C3H mice fed a high fat diet.
The antioxidant tempol transforms gut microbiome to resist obesity in female C3H mice fed a high fat diet.
复制标题
DOI：
10.1016/j.freeradbiomed.2021.12.006
复制
发表时间：
2022-01
影响因子：
7.4
通讯作者：
Cook JA
中科院分区：
文献类型：
--
作者：
Choudhuri R;Sowers AL;Chandramouli GVR;Gamson J;Krishna MC;Mitchell JB;Cook JA
氮氧化合物Tempol可防止喂食高脂饮食（HFD）的小鼠发生肥胖相关变化。本研究的目的是深入了解Tempol在雌性C3 H小鼠中导致这种变化的机制。使用微阵列方法、蛋白质印迹、胆汁酸分析和肠道微生物组测序来鉴定HFD雌性C3 H小鼠中受Tempol调控的多种基因、蛋白质、胆汁酸和细菌。还研究了抗生素与Tempol组合对肠道微生物区系的影响。使用靶向基因微阵列分析来自Tempol处理的小鼠的脂肪组织，揭示了脂肪酸代谢基因的上调（Acadm和Acadl > 4倍，Acsm 3和Acsm 5> 10倍）。从HFD切换到Tempol HFD的小鼠肝组织的基因微阵列研究显示脂肪酸合成基因下调和脂肪酸氧化基因上调。对肥胖相关蛋白的分析表明，Tempol HFD改变了乙醛脱氢酶1A 1（ALDH 1A 1）和禁食诱导的脂肪因子/血管生成素样蛋白4（FIAF/ANGPTL 4）的表达。胆汁酸研究显示Tempol处理小鼠的肝脏和血清中的胆酸（CA）和脱氧胆酸（DCA）增加。Tempol HFD对肠道微生物组组成的影响显示嗜粘蛋白阿克曼氏菌（Akkermansia muciniphila）的种群增加，这是一种已知与瘦的抗炎表型相关的细菌物种。抗生素处理显著降低了细菌数量的总水平，然而，Tempol在降低HFD体重增加方面仍然有效。即使在抗生素治疗后，Tempol仍然对几种细菌物种如嗜粘蛋白阿克曼氏菌和瓦氏嗜菌有积极影响。Tempol减缓喂食HFD的雌性小鼠体重增加的积极作用涉及肠道微生物组，胆汁酸组成的变化，以及最终涉及脂肪酸代谢和储存的基因和蛋白质的变化。
The nitroxide, Tempol, prevents obesity related changes in mice fed a high fat diet (HFD). The purpose of this study was to gain insight into the mechanisms that result in such changes by Tempol in female C3H mice. Microarray methodology, Western blotting, bile acid analyses, and gut microbiome sequencing were used to identify multiple genes, proteins, bile acids, and bacteria that are regulated by Tempol in female C3H mice on HFD. The effects of antibiotics in combination with Tempol on the gut microflora were also studied. Adipose tissue, from Tempol treated mice, was analyzed using targeted gene microarrays revealing up-regulation of fatty acid metabolism genes (Acadm and Acadl > 4-fold, and Acsm3 and Acsm5 > 10-fold). Gene microarray studies of liver tissue from mice switched from HFD to Tempol HFD showed down-regulation of fatty acid synthesis genes and up-regulation of fatty acid oxidation genes. Analyses of proteins involved in obesity revealed that the expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and fasting induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4) was altered by Tempol HFD. Bile acid studies revealed increases in cholic acid (CA) and deoxycholic acid (DCA) in both the liver and serum of Tempol treated mice. Tempol HFD effect on the gut microbiome composition showed an increase in the population of Akkermansia muciniphila, a bacterial species known to be associated with a lean, anti-inflammatory phenotype. Antibiotic treatment significantly reduced the total level of bacterial numbers, however, Tempol was still effective in reducing the HFD weight gain. Even after antibiotic treatment Tempol still positively influenced several bacterial species such as as Akkermansia muciniphila and Bilophila wadsworthia. The positive effects of Tempol moderating weight gain in female mice fed a HFD involves changes to the gut microbiome, bile acids composition, and finally to changes in genes and proteins involved in fatty acid metabolism and storage.
登录
查看更多内容
影响因子：
7.4
作者：
Samuni, Yuval;Cook, John A.;Choudhuri, Rajani;DeGraff, William;Sowers, Anastasia L.;Krishna, Murali C.;Mitchell, James B.
通讯作者：
Mitchell, James B.
视网膜甲醛脱氢酶1调节白色脂肪组织中的热程序。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Fisher, RA;Corbet, AS;Williams, CB
通讯作者：
Williams, CB
影响因子：
8.2
作者：
Janssen AWF;Katiraei S;Bartosinska B;Eberhard D;Willems van Dijk K;Kersten S
通讯作者：
Kersten S
DOI：
10.1016/j.apsb.2015.01.004
发表时间：
2015-03
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Ding L;Yang L;Wang Z;Huang W
通讯作者：
Huang W