Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Physiol Behav. 2012 Mar 20;105(5):1182-93. doi: 10.1016/j.physbeh.2011.12.010. Epub 2011 Dec 22.
Since the introduction of the thrifty phenotype hypothesis, the potential traits of thrift have been described in increasingly broad terms but biochemical and behavioral evidence of thrift has not been well demonstrated. The objective of our studies was to use a rodent model to identify features of thrift programmed by early life protein restriction. Robust programming of thrifty features requires a thrifty nutritional environment during the entire window of developmental plasticity. Therefore, pregnant rats were exposed to a low protein diet throughout the window of developmental plasticity spanning the period of gestation and lactation and its effects on energy acquisition, storage and expenditure in the adult offspring were examined. Maternal protein restriction reduced birth weight and produced long term reductions in body and organ weights in the offspring. Low protein offspring demonstrated an increased drive to seek food as evidenced by hyperphagia that was mediated by changes in plasma leptin and ghrelin levels. Hyperphagia was accompanied by increased efficiency in converting caloric intake into body mass. The higher feed efficiency was mediated by greater insulin sensitivity. Energy expenditure of low protein offspring in locomotion was not affected either in the light or dark phase. However, low protein offspring exhibited higher resting and basal metabolic rates as evidenced by higher core body temperature in the fed and fasted states. The increased thermogenesis was not mediated by thyroid hormones but by an increased sympathetic nervous system drive as reflected by a lower areal bone mineral density and bone mineral content and lower plasma adiponectin and triglyceride levels. Elevated thermogenesis in the low protein offspring possibly offsets the effects of hyperphagia, minimizes their chances of weight gain, and improves survivability. This constellation of metabolic features in the low protein offspring will maximize survival potential in a post natal environment of nutritional scarcity and constitute a thrifty phenotype.
自从节俭表型假说提出以来，节俭的潜在特征已经被越来越广泛地描述，但节俭的生化和行为证据尚未得到很好的证明。我们的研究目的是使用啮齿动物模型来确定早期蛋白质限制编程的节俭特征。节俭特征的稳健编程需要在整个发育可塑性窗口中提供节俭的营养环境。因此，怀孕的老鼠在整个发育可塑性窗口中暴露于低蛋白饮食中，跨越妊娠和哺乳期，检查其对成年后代能量获取、储存和支出的影响。母体蛋白质限制降低了出生体重，并导致后代长期减少体重和器官重量。低蛋白后代表现出更高的觅食动力，表现为贪食症，这是由血浆瘦素和 ghrelin 水平的变化介导的。贪食症伴随着将卡路里摄入转化为体重的效率增加。低蛋白后代的更高饲料效率是由更高的胰岛素敏感性介导的。低蛋白后代在运动中的能量消耗无论是在亮期还是暗期都没有受到影响。然而，低蛋白后代表现出更高的静息和基础代谢率，表现为在进食和禁食状态下核心体温更高。增加的产热不是由甲状腺激素介导的，而是由增加的交感神经系统驱动介导的，表现为更低的骨面积骨密度和骨矿物质含量以及更低的血浆脂联素和甘油三酯水平。低蛋白后代的产热增加可能抵消了贪食症的影响，最大限度地减少了体重增加的机会，并提高了存活率。低蛋白后代的这种代谢特征组合将最大限度地提高其在营养匮乏的产后环境中的生存潜力，并构成节俭表型。
