Baker M S, Li G, Kohorst J J, Waterland R A
Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
1] Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, TX, USA [2] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Int J Obes (Lond). 2015 Jan;39(1):98-104. doi: 10.1038/ijo.2013.146. Epub 2013 Aug 8.
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.
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.
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.
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.
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.
产前和产后早期关键时期的环境暴露会影响哺乳动物体重调节机制的发育，影响肥胖的终生风险。然而，介导此类影响持续性的具体生物学过程仍知之甚少。
本研究的目的是确定先前报道的肥胖黄刺鼠（A(vy)/a）母亲后代中促进肥胖作用的发育时间和生理基础。
肥胖A(vy)/a和瘦型（a/a）母亲的新生后代在出生后不久进行交叉寄养，以分别研究子宫内或哺乳期暴露于A(vy)/a母鼠的影响。在断奶后不久和成年期测量后代的身体成分、食物摄入量、身体活动和能量消耗。
肥胖A(vy)/a母鼠的后代出现了矛盾的胎儿生长受限，随后成年后肥胖，尤其是雌性。我们的主要分析集中在野生型（a/a）后代上，因为一部分成年A(vy)/a后代患上了一种类似于糖尿病肾病的肾脏疾病。详细的生理特征表明，断奶后不久和成年期，A(vy)/a母亲所生的雌性野生型小鼠并非食欲亢进，而是身体活动和能量消耗减少。在雄性后代中未检测到这种协调变化。对我们纵向数据的中介回归分析支持了一条因果途径，即胎儿生长受限持续降低身体活动，导致成年肥胖。
我们的数据与最近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有女性特异性影响，并提供了新的机制见解，即这可能是通过一个人固有身体活动倾向的永久性和性别特异性变化而发生的。
