Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet.
Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet.
复制标题
DOI：
10.14814/phy2.12336
复制
发表时间：
2015-03
影响因子：
2.5
通讯作者：
Lane M
中科院分区：
文献类型：
--
作者：
Fullston T;McPherson NO;Owens JA;Kang WX;Sandeman LY;Lane M
肥胖和相关合并症在全球范围内变得越来越普遍。在小鼠受孕前，父亲暴露于高脂肪饮食（HFD）损害雄性后代的代谢和生殖健康，尽管他们的控制饮食（CD）消费。然而，后代与父母分享生活方式，包括饮食。我们评估了来自HFD父亲的雄性后代是否对HFD诱导的代谢和生殖紊乱具有更高的易感性。在2 × 2设计中，创始雄性（F0）及其后代（F1）喂食HFD或营养匹配的CD。无论父亲的饮食，HFD喂养的雄性后代有更大的总体重和肥胖。与CD亲代/喂食同窝仔相比，HFD雄性子代和喂食HFD的子代体重最重，肥胖最严重，血清胆固醇、甘油三酯、HDL和NEFA浓度最高。血清胰岛素的协同增加被父亲/儿子的HFD消耗所掩盖，伴随着血清葡萄糖的增加。无论是父亲或后代HFD与后代精子活力的类似减少。而精子ROS浓度和精子-卵母细胞结合均受到F0 HFD和F1 HFD的不利影响，两者之间存在明显的相互作用，最终导致该组中受损最严重的精子参数。这表明，代谢和生育能力的障碍，在男性后代的父系HFD父亲加剧了“第二次打击”暴露于相同的致肥胖环境出生后。如果可以转化为人类健康，这表明不良的生殖和代谢结果可能会通过共同的卡路里密集饮食在几代人之间放大，这与当前全球肥胖流行病有关。
Obesity and related comorbidities are becoming increasingly prevalent globally. In mice preconception paternal exposure to a high fat diet (HFD) impairs the metabolic and reproductive health of male offspring, despite their control diet (CD) consumption. However, offspring share lifestyle, including diet, with parents. We assessed if male offspring from HFD fathers have a heightened susceptibility to HFD-induced metabolic and reproductive derangements. This 2 × 2 design saw founder males (F0) and their offspring (F1) fed either a HFD or a nutritionally matched CD. Regardless of paternal diet, HFD fed male offspring had greater total body weight and adiposity. Offspring sired by a HFD male and fed a HFD were the heaviest, had the greatest adiposity and had the greatest concentration of serum cholesterol, triglyceride, HDL, and NEFA compared with CD sired/fed littermates. A synergistic increase in serum insulin was unmasked by both father/son HFD consumption, concomitant with increased sera glucose. Either a paternal or offspring HFD was associated with similar reductions to offspring sperm motility. Whereas sperm ROS concentrations and sperm–oocyte binding saw detrimental effects of both F0 HFD and F1 HFD with an interaction evident between both, culminating in the most impaired sperm parameters in this group. This indicates that metabolic and fertility disturbances in male offspring sired by HFD fathers are exacerbated by a “second-hit” of exposure to the same obesogenic environment postnatally. If translatable to human health, this suggests that adverse reproductive and metabolic outcomes may be amplified across generations through a shared calorie dense diet, relevant to the current worldwide obesity epidemic.