Department of Microscopy, Laboratory of Cell Biology, and Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.
Department of Genetics, Faculty of Medicine of the University of Porto, Porto, Portugal.
Am J Physiol Endocrinol Metab. 2020 Dec 1;319(6):E1061-E1073. doi: 10.1152/ajpendo.00235.2020. Epub 2020 Oct 12.
Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health, but few studies have addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism, leading to permanent damage to sperm parameters. After weaning ( after birth), 36 male mice were randomly divided into three groups and fed with a different diet regimen for 200 days: a standard chow diet (CTRL), a high-fat diet (HFD) (carbohydrate: 35.7%, protein: 20.5%, and fat: 36.0%), and a high-fat diet for 60 days, then replaced by standard chow (HFD). Biometric and metabolic data were monitored. Animals were then euthanized, and tissues were collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Our results show that mice fed with a high-fat diet, even if only until early adulthood, had lower sperm viability and motility, and higher incidence of head and tail defects. Although diet reversion with weight loss during adulthood prevents the progression of metabolic syndrome, testicular content in fatty acids is irreversibly affected. Excessive fat intake promoted an overaccumulation of proinflammatory n-6 polyunsaturated fatty acids in the testis, which is strongly correlated with negative effects upon sperm quality. Therefore, the adoption of high-fat diets during early life correlates with irreversible changes in testicular lipid content and metabolism, which are related to permanent damage to sperm quality later in life.
儿童肥胖是一个严重的问题，与晚年健康不良有关。新出现的数据表明，肥胖对男性的性健康和生殖健康有长期的不良影响，但很少有研究涉及这个问题。我们假设，在生命早期暴露于高脂肪饮食会改变睾丸的脂质含量和代谢，导致精子参数的永久性损伤。断奶后（出生后），36 只雄性小鼠被随机分为三组，并接受不同的饮食方案喂养 200 天：标准饮食（CTRL）、高脂肪饮食（HFD）（碳水化合物：35.7%，蛋白质：20.5%，脂肪：36.0%）和高脂肪饮食 60 天，然后更换为标准饮食（HFD）。监测生物计量和代谢数据。然后将动物安乐死，并收集组织。评估附睾精子参数和内分泌参数。提取睾丸代谢物，并通过 1H-NMR 和 GC-MS 进行鉴定。评估睾丸线粒体和抗氧化活性。我们的结果表明，即使只在成年早期喂养高脂肪饮食，小鼠的精子活力和运动能力也会降低，头部和尾部缺陷的发生率也会更高。虽然在成年期通过减肥恢复正常饮食可以防止代谢综合征的进展，但睾丸内的脂肪酸含量仍受到不可逆转的影响。过量的脂肪摄入会促进睾丸内促炎的 n-6 多不饱和脂肪酸过度积累，这与精子质量的负面影响密切相关。因此，在生命早期采用高脂肪饮食与睾丸脂质含量和代谢的不可逆转变化相关，这与晚年精子质量的永久性损伤有关。
