背景:肥胖母体的子代,有些代谢基因在某些环境影响下处于"沉默"状态,这些"沉默"的基因可能因后天环境的影响又被"唤醒",继而引起代谢调控紊乱. 目的:雄性子代在不同饮食结构的情况下,探索母鼠长期高脂和运动干预的代谢遗传效应. 方法:3周龄雌性C57BL/6小鼠70只,随机分成高脂安静组与高脂运动组,干预16周后自然分娩.2组在4周哺乳期结束后,各随机抽取子代雄性小鼠16只,共32只分为4组:高脂安静-高脂组、高脂运动-高脂组、高脂安静-普食组、高脂运动-普食组,分别给予6周高脂喂养或普食喂养.子代在第10周进行葡萄糖耐量试验与胰岛素耐量试验,随后进行体成分分析及取材.肝脏蛋白免疫印迹测定p-Akt水平;下丘脑弓状核免疫荧光分析神经肽Y和阿黑皮素的表达情况. 结果与结论:①在高脂饮食模式下,与高脂安静组相比,高脂运动组子代小鼠的糖代谢能力、体质量、体成分等都有显著性改善(P<0.05);②在普食饮食模式下,与高脂安静组相比,高脂运动组子代小鼠下丘脑弓状核的神经肽Y表达量显著下降(P<0.05),阿黑皮素表达显著上调(P<0.05),肝脏Akt(Ser473)磷酸化蛋白表达在胰岛素(-)的情况下无显著性差异,但在胰岛素(+)的情况下组间差异有显著性意义(P<0.05);③结果说明,子代在高脂模式下,母体长期运动获得的代谢保护效应可能会随着子代高脂暴露时间的延长而逐渐弱化;子代在普食模式下,母代长期的运动可以改善雄性子代能量代谢的中枢调控和胰岛素的敏感性.
BACKGROUND:In the offspring of obese mothers,some metabolic genes are"silent"under certain environmental influences.These"silent"genes may be"awakened"under the acquired environment and then cause metabolic regulation disorders. OBJECTIVE:In the case of offspring with different diets,to explore the metabolic genetic effects of long-term high-fat and exercise intervention in female mice. METHODS:Seventy 3-week-old female C57BL/6 mice were divided into high-fat diet(HFD)and high-at exercise groups(high-fat diet+exercise,HFD-Ex),and they gave birth naturally after 16 weeks of intervention.After 4-week lactation,16 male offspring mice from each group were randomly selected.Totally 32 offspring mice were randomly divided into 4 subgroups and given high-fat diet or standard chow diet for 6 weeks:HFD-HFD,HFD-Ex-HFD,HFD-standard chow diet,and HFD-Ex-standard chow diet.The offspring mice were subjected to glucose tolerance test and insulin tolerance test in the 10th week,followed by body composition analysis and sacrifice.Western blot was used to determine the level of p-Akt in the liver.Immunofluorescence of the hypothalamic arcuate nucleus was used to analyze the expression of neuropeptide Y and pro-opiomelanocortion. RESULTS AND CONCLUSION:Under the high-fat diet,compared with the HFD group,the offspring of the HFD-Ex group had significantly improvements in glucose metabolism,body mass,and body composition(P<0.05).Under the standard chow diet,compared with the HFD group,the expression of neuropeptide Y in the hypothalamic arcuate nucleus of the HFD-Ex group was significantly decreased(P<0.05),and the expression of pro-opiomelanocortion was significantly up-regulated(P<0.05).In the case of insulin(-),the expression of phosphorylated Akt(Ser473)protein in the liver showed no significant difference between the two groups,but in the case of insulin(+),there was a significant difference between the two groups(P<0.05).In the high-fat diet mode,the metabolic protection effect of the maternal long-term exercise may gradually weaken with the prolongation of the offspring's high-fat exposure;in the standard chow diet mode,the maternal long-term exercise can improve the central regulation of energy metabolism and insulin sensitivity of the male offspring.