Combined maternal and post-weaning high fat diet inhibits male offspring's prostate cancer tumorigenesis in transgenic adenocarcinoma of mouse prostate model
Combined maternal and post-weaning high fat diet inhibits male offspring's prostate cancer tumorigenesis in transgenic adenocarcinoma of mouse prostate model
复制标题
母体和断奶后高脂肪饮食相结合抑制转基因小鼠前列腺模型雄性后代前列腺癌肿瘤发生
DOI：
10.1002/pros.23760
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发表时间：
2019-04-01
期刊：
影响因子：
2.8
通讯作者：
Jiang, Haowen
中科院分区：
文献类型：
--
作者：
Liu, Yufei;Wu, Xiaobo;Jiang, Haowen
背景高脂肪饮食及其肠道菌群的反应性变化与人类和动物的许多疾病有关。但是母体和断奶后HFD如何影响雄性后代前列腺癌（PCa）的肿瘤发生尚未报道。方法采用转基因小鼠前列腺腺癌（TRAMP）模型，研究母体或/和断奶后HFD对子代前列腺肿瘤发生的单独和联合影响。雄性TRAMP小鼠（n=24）分别饲喂对照组和高脂饲料喂养，断奶后再饲喂对照组和高脂饲料喂养。28周处死所有小鼠。行前列腺组织病理学检查。粪便16S rRNA焦磷酸测序法分析肠道菌群，LC-MS/MS法测定血清代谢产物。结果断奶后HFD能显著促进子代前列腺癌的发生（P=0.031），而母体HFD组的结果相似，但差异无统计学意义（P=0.056）。而母体和断奶后HFD联合使用可显著降低子代PCa的发生（P=0.019）。各组间特定微生物种群和血清代谢物存在显著差异。例如，母系和断奶后混合HFD的小鼠肠道中绒螺旋科、玫瑰属和Amycolatopsis的丰度更高，血清中l -蛋氨酸增加（P=0.0052），血清中-亚麻酸（P=0.0052）降低（P=0.0052）
BackgroundHigh fat diet (HFD) and its responsive change of gut microbiota are associated with numerous diseases in human and animal studies. But how maternal and post-weaning HFD may influence the tumorigenesis of prostate cancer (PCa) in male offspring has not yet been reported.MethodsWe studied both solitary and combined effects of maternal or/and post-weaning HFD on the tumorigenesis of prostate in offspring using a transgenic adenocarcinoma of mouse prostate (TRAMP) model. TRAMP male mice (n=24) were born to and fostered onto control diet or HFD-fed mothers, the weaned pups were further fed control or fat diet. All mice were sacrificed at the 28th week. The prostate histopathology was performed. The gut microbiota was analyzed by fecal 16S rRNA pyrosequencing, and the serum metabolites were determined by LC-MS/MS.ResultsOur results indicated that post-weaning HFD could significantly promote the PCa tumorigenesis in offspring (P=0.031), and similar results were found in maternal HFD group but with no significant differences (P=0.056). However, combined maternal and post-weaning HFD could significantly reduce the PCa tumorigenesis in offspring (P=0.019). Significant differences in specific microbial populations and serum metabolites were observed across groups. For example, mice with combined maternal and post-weaning HFD had higher abundance of gut Lachonospiraceae, Roseburia, and Amycolatopsis, increased serum L-methionine (P=0.0052), and decreased serum -linolenic acid (P