Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC, Australia.
The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, Australia.
J Physiol. 2019 Jan;597(1):121-136. doi: 10.1113/JP276386. Epub 2018 Nov 22.
A paternal high-fat diet/obesity before mating can negatively influence the metabolism of offspring. Exercise only early in life has a remarkable effect with respect to reprogramming adult rat offspring exposed to detrimental insults before conception. Exercise only early in life normalized adult whole body and muscle insulin resistance as a result of having a high-fat fed/obese father. Unlike the effects on the muscle, early exercise did not normalize the reduced adult pancreatic beta cell mass as a result of having a high-fat fed/obese father. Early-life exercise training may be able to reprogram an individual whose father was obese, inducing long-lasting beneficial effects on health.
A paternal high-fat diet (HFD) impairs female rat offspring glucose tolerance, pancreatic morphology and insulin secretion. We examined whether only 4 weeks of exercise early in life could reprogram these negative effects. Male Sprague-Dawley rats consumed a HFD for 10 weeks before mating with chow-fed dams. Female offspring remained sedentary or performed moderate intensity treadmill exercise (5 days week , 60 min day , 20 m min ) from 5 to 9 weeks of age. Paternal HFD impaired (P < 0.05) adult offspring whole body insulin sensitivity (i.p. insulin sensitivity test), as well as skeletal muscle ex vivo insulin sensitivity and TBC1D4 phosphorylation. It also lowered β-cell mass and reduced in vivo insulin secretion in response to an i.p. glucose tolerance test. Early-life exercise in offspring reprogrammed the negative effects of a paternal HFD on whole body insulin sensitivity, skeletal muscle ex vivo insulin-stimulated glucose uptake and TBC1D4 phosphorylation and also increased glucose transporter 4 protein. However, early exercise did not normalize the reduced pancreatic β-cell mass or insulin secretion. In conclusion, only 4 weeks of exercise early in life in female rat offspring reprograms reductions in insulin sensitivity in adulthood caused by a paternal HFD without affecting pancreatic β-cell mass or insulin secretion.
交配前雄性高脂肪饮食/肥胖会对后代的新陈代谢产生负面影响。仅在生命早期进行锻炼对受孕前受到有害刺激的成年大鼠后代具有显著的重编程效果。仅在生命早期进行锻炼可使由于高脂肪饮食/肥胖父亲而导致的成年全身和肌肉胰岛素抵抗正常化。与肌肉的作用不同，早期运动并不能使由于高脂肪饮食/肥胖父亲而导致的成年胰腺β细胞质量减少正常化。早期的运动训练可能能够对其父亲肥胖的个体进行重编程，从而对健康产生持久的有益影响。
雄性高脂肪饮食（HFD）会损害雌性大鼠后代的葡萄糖耐量，胰腺形态和胰岛素分泌。我们检查了仅在生命早期进行 4 周的运动是否可以重编程这些负面影响。雄性 Sprague-Dawley 大鼠在与喂食标准饮食的母鼠交配前，连续 10 周食用 HFD。雌性后代保持久坐不动或从 5 至 9 周龄开始进行中等强度的跑步机运动（每周 5 天，每天 60 分钟，20 米/分钟）。父代 HFD 损害了（P<0.05）成年后代的全身胰岛素敏感性（腹腔内胰岛素敏感性测试），以及骨骼肌的体外胰岛素敏感性和 TBC1D4 磷酸化。它还降低了β细胞质量，并降低了对腹腔内葡萄糖耐量测试的胰岛素分泌反应。后代的早期运动重编程了父代 HFD 对全身胰岛素敏感性，骨骼肌体外胰岛素刺激的葡萄糖摄取和 TBC1D4 磷酸化的负面影响，并且还增加了葡萄糖转运蛋白 4 蛋白。但是，早期运动并没有使减少的胰岛β细胞质量或胰岛素分泌正常化。总之，雌性大鼠后代仅在生命早期进行 4 周的运动可重编程由父代 HFD 引起的成年后胰岛素敏感性降低，而不会影响胰岛β细胞质量或胰岛素分泌。
