U.S. Department of Agriculture Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA.
U.S. Department of Agriculture Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA.
J Nutr Biochem. 2018 Jul;57:35-44. doi: 10.1016/j.jnutbio.2018.03.013. Epub 2018 Mar 21.
Paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes (T2D) risk; however, no studies have determined whether a paternal high-fat (HF) diet and exercise interact to alter offspring body weight (BW), adiposity and T2D risk. Three-week-old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or an HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF-diet-fed dams. After weaning, male offspring were fed an NF or HF diet for an additional 3 months. F1 male mice whose fathers ate an HF diet had decreased % body fat accompanied by decreased gene expression of beige adipocyte marker FGF21. However, paternal HF-diet-induced reductions in F1 offspring % body fat normalized but did not reduce T2D risk. Exercise was protective against paternal HF-diet-induced insulin resistance by increasing the expression of insulin signaling (GLUT4, IRS1 and PI3K) markers in skeletal muscle resulting in normal T2D risk. When fathers were fed an HF diet and exercised, a postnatal HF diet increased beiging (PPARγ). Thus, these findings show that increases in T2D risk in male offspring when the father consumes an HF diet can be normalized when the father also exercises preconception and that this protection may occur by increases in insulin signaling potential within offspring skeletal muscle. Future studies should further determine the physiological mechanism(s) underlying the beneficial effects of exercise through the paternal lineage.
父亲肥胖增加，而父亲运动减少，后代肥胖和 2 型糖尿病（T2D）风险；然而，尚无研究确定父亲高脂肪（HF）饮食和运动是否相互作用以改变后代体重（BW）、肥胖和 T2D 风险。3 周龄雄性 C57BL/6 小鼠喂食正常脂肪（NF）饮食（16%脂肪）或高脂肪（HF）饮食（45%脂肪），并在与 NF 饮食喂养的母鼠交配前进行 3 个月的自愿轮跑运动或笼内活动。断奶后，雄性后代再喂食 NF 或 HF 饮食 3 个月。父亲食用 HF 饮食的 F1 雄性小鼠体脂肪百分比降低伴随着米色脂肪标记物 FGF21 的基因表达降低。然而，父亲 HF 饮食引起的 F1 后代体脂肪百分比降低得到了正常化，但并未降低 T2D 风险。运动通过增加骨骼肌中胰岛素信号（GLUT4、IRS1 和 PI3K）标志物的表达来预防父亲 HF 饮食引起的胰岛素抵抗，从而导致正常的 T2D 风险。当父亲食用 HF 饮食并运动时，产后 HF 饮食会增加米色化（PPARγ）。因此，这些发现表明，当父亲食用 HF 饮食时，雄性后代的 T2D 风险增加可以在父亲在受孕前也进行运动时得到正常化，而这种保护可能是通过增加后代骨骼肌中的胰岛素信号潜力来实现的。未来的研究应该进一步确定通过父系途径运动的有益效果的生理机制。
