Fetal growth restriction promotes physical inactivity and obesity in female mice
Fetal growth restriction promotes physical inactivity and obesity in female mice
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DOI：
10.1038/ijo.2013.146
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发表时间：
2015-01-01
影响因子：
4.9
通讯作者：
Waterland, R. A.
中科院分区：
文献类型：
--
作者：
Baker, M. S.;Li, G.;Waterland, R. A.
背景技术背景：在产前和产后早期的关键时期，环境暴露会影响哺乳动物体重调节机制的发育，从而影响终身肥胖的风险。然而，介导这种效应持续存在的特定生物学过程仍然知之甚少。目的：本研究的目的是确定先前报道的肥胖型黄曲霉菌（A（vy）/a）母亲的后代中促肥胖效应的发育时间和生理基础。设计：出生后不久，将肥胖A（vy）/a和瘦（a/a）母亲的新生儿交叉培养，分别研究子宫内或哺乳期暴露于A（vy）/a母鼠的影响。体成分，食物摄入量，体力活动和能量消耗测定在后代断奶后不久，在adult.Results：后代的肥胖A（vy）/a母鼠矛盾地经历了胎儿生长受限，其次是成年发病的肥胖症，特别是在女性。我们的主要分析集中在野生型（a/a）后代，因为成年A（vy）/a后代的一个子集感染了类似糖尿病肾病的肾脏疾病。详细的生理特征表明，无论是断奶后不久，在成年期，雌性野生型小鼠出生的A（vy）/a母亲是不是hyperphagic，但减少了体力活动和能量消耗。在雄性后代中没有检测到这种协调的变化。对我们纵向数据的中介回归分析支持一种因果途径，即胎儿生长受限持续减少体力活动，导致成人肥胖。我们的数据与最近的几项人类流行病学研究一致，这些研究表明围产期营养限制对后期肥胖的女性特异性影响，并提供了一种新的机制性见解，即这可能通过一个人固有的身体活动倾向的永久性和性别特异性变化而发生。
BACKGROUND: Environmental exposures during critical periods of prenatal and early postnatal life affect the development of mammalian body weight regulatory mechanisms, influencing lifelong risk of obesity. The specific biological processes that mediate the persistence of such effects, however, remain poorly understood.OBJECTIVE: The objectives of this study were to determine the developmental timing and physiological basis of the obesity-promoting effect previously reported in offspring of obese agouti viable yellow (A(vy)/a) mothers.DESIGN: Newborn offspring of obese A(vy)/a and lean (a/a) mothers were cross-fostered shortly after birth to study separately the effects of in utero or suckling period exposure to A(vy)/a dams. Body composition, food intake, physical activity and energy expenditure were measured in offspring shortly after weaning and in adulthood.RESULTS: Offspring of obese A(vy)/a dams paradoxically experienced fetal growth restriction, which was followed by adult-onset obesity specifically in females. Our main analyses focused on wild-type (a/a) offspring, because a subset of adult A(vy)/a offspring contracted a kidney disease resembling diabetic nephropathy. Detailed physiological characterization demonstrated that, both shortly after weaning and in adulthood, female wild-type mice born to A(vy)/a mothers are not hyperphagic but have reduced physical activity and energy expenditure. No such coordinated changes were detected in male offspring. Mediational regression analysis of our longitudinal data supported a causal pathway in which fetal growth restriction persistently reduces physical activity, leading to adult obesity.CONCLUSIONS: Our data are consistent with several recent human epidemiological studies showing female-specific effects of perinatal nutritional restriction on later obesity, and provide the novel mechanistic insight that this may occur via permanent and sex-specific changes in one's inherent propensity for physical activity.