Paternal low protein diet perturbs inter-generational metabolic homeostasis in a tissue-specific manner in mice.

Paternal low protein diet perturbs inter-generational metabolic homeostasis in a tissue-specific manner in mice.
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DOI:
10.1038/s42003-022-03914-8
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发表时间:
2022-09-08
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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--
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在后代中驱动父源性程序性代谢疾病的潜在机制仍然不清楚。我们给雄性C57 BL/6小鼠喂食对照正常蛋白质饮食(NPD; 18%蛋白质)或等热量低蛋白质饮食(LPD; 9%蛋白质)至少8周。使用人工授精,结合输精管切除的男性交配,我们产生的后代使用NPD或LPD精子,但在NPD或LPD精浆的存在下。无论是LPD精子或精液的后代显示体重升高和组织血脂异常,从3周龄。这些变化在成年期变得更加明显,与改变的肝脏代谢和炎症途径基因表达一起发生。第二代后代也显示差异组织脂质丰度,与第一代成人的配置文件相似。这些研究结果表明,后代的代谢动态平衡受到干扰,在响应一个次优的父亲饮食的影响仍然明显的第二代。不良的父亲饮食导致后代组织脂质丰度的变化,这种变化在第二代中仍然很明显。
The underlying mechanisms driving paternally-programmed metabolic disease in offspring remain poorly defined. We fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. Using artificial insemination, in combination with vasectomised male mating, we generated offspring using either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Offspring from either LPD sperm or seminal fluid display elevated body weight and tissue dyslipidaemia from just 3 weeks of age. These changes become more pronounced in adulthood, occurring in conjunction with altered hepatic metabolic and inflammatory pathway gene expression. Second generation offspring also display differential tissue lipid abundance, with profiles similar to those of first generation adults. These findings demonstrate that offspring metabolic homeostasis is perturbed in response to a suboptimal paternal diet with the effects still evident within a second generation. Poor paternal diet leads to changes in offspring tissue lipid abundance that is still evident in a second generation.
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