Biological Chemistry Group, Jodrell Laboratory, RBG Kew, Kew Road, Richmond, Surrey TW9 3AB, UK.
Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road, Cambridge CB2 0QQ, UK.
Int J Mol Sci. 2023 Jan 17;24(3):1814. doi: 10.3390/ijms24031814.
There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein-high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, 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. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring's hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner.
越来越多的证据表明，在受孕时，父亲不良的饮食会增加后代在成年后患一系列非传染性代谢疾病的风险，如肥胖、糖尿病和心血管疾病。我们假设，父亲低蛋白高碳水化合物的饮食会通过精子和精液介导的机制扰乱后代组织的脂质丰度。为了验证我们的假设，我们用 18%蛋白质的正常蛋白饮食（NPD）或等热量的低蛋白饮食（LPD）喂养 C57BL/6 雄性小鼠至少 8 周。我们通过人工授精，结合去势雄性交配，产生后代。通过这种方法，我们得到了来自 NPD 或 LPD 精子的后代，但存在 NPD 或 LPD 精液。利用高分辨率质谱法，我们发现，从 LPD 精子或精液中得到的后代，从 3 周龄开始，心脏和大脑的脂质丰度就发生了紊乱，通常与组织甘油三酯的丰度改变有关。我们还观察到对照组和实验组后代心脏和大脑中脂质的性别特异性差异模式。这些观察结果表明，在受孕时，父亲不良的饮食会以年龄、性别和代际特异性的方式影响后代心脏和大脑的脂质谱。
