School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK; and Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, UK
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK; and.
Am J Physiol Heart Circ Physiol. 2014 May 15;306(10):H1444-52. doi: 10.1152/ajpheart.00981.2013. Epub 2014 Mar 21.
Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD) on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein) or LPD (9% casein) for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03) and increased male offspring weight (P = 0.009) were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P < 0.02). However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg) and elevated heart rate (P < 0.05), whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk), LPD males had elevated adiposity (P = 0.04), reduced heart-to-body weight ratio (P = 0.04), and elevated circulating TNF-α levels (P = 0.015) compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb) and metabolism (Fto) in LPD offspring (P < 0.03). These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.
虽然母体受孕前饮食与成年后代健康之间的关联已得到充分描述，但我们对父体在受孕时的营养对后代表型的影响的理解仍不清楚。因此，我们在小鼠中确定了父体受孕前低蛋白饮食（LPD）对成年后代心血管和代谢健康的影响。雄性 C57BL/6 小鼠在交配前分别用正常蛋白饮食（NPD；18%酪蛋白）或 LPD（9%酪蛋白）喂养 7 周。与 NPD 研究雄性相比，LPD 组的后代中雄性与雌性的比例降低（P=0.03），雄性后代体重增加（P=0.009），但平均窝仔数没有差异。LPD 后代在 2 周和 3 周龄时比 NPD 后代更重（P<0.02）。然而，之后没有观察到体重的差异。来自 LPD 研究雄性的成年雄性后代表现出相对低血压（降低 9.2mmHg）和心率升高（P<0.05），而雄性和雌性后代均表现出血管功能障碍和葡萄糖耐量受损，与 NPD 后代相比。在淘汰时（24 周），与 NPD 雄性相比，LPD 雄性的肥胖程度增加（P=0.04），心脏与体重的比值降低（P=0.04），循环 TNF-α水平升高（P=0.015）。LPD 后代心脏和肝脏组织中涉及钙信号（Adcy、Plcb、Prkcb）和代谢（Fto）的基因的转录表达降低（P<0.03）。这些新数据揭示了次优父体营养对成年后代心血管和代谢稳态的影响，并提供了一些潜在的调控机制的见解。
