Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
Laboratorio de Células troncales y Biología del Desarrollo, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
J Comp Physiol B. 2023 Dec;193(6):677-688. doi: 10.1007/s00360-023-01520-6. Epub 2023 Oct 13.
Fetal metabolic programming produced by unfavorable prenatal nutritional conditions leads to the development of a disorder called "thrifty phenotype", which is associated with pathologies such as diabetes and obesity in adulthood. However, from an ecophysiological approach, few studies have addressed the development of thrifty phenotypes in terms of energy. This might represent an adaptive advantage against caloric deficiency conditions extending into adulthood. The objective of this study is to investigate the potential adaptive value of the thrifty phenotype expression through prenatal programming in a rodent model experiencing varying dietary conditions in different temporal contexts. To fill this gap, adult males of Mus musculus (BALB/C) from two maternal pregnancy groups were analyzed: control (ad libitum feeding) and caloric restriction from day 10 of gestation (70% restriction). Adult offspring of these groups were split further for two experiments: acute food deprivation and chronic caloric restriction at 60%. The acute food deprivation was performed for 24, 48 or 72 h while the caloric restriction regime was sustained for 20 days. For each experiment, morphological variables, such as body and organ mass, and gene expression related to lipid and carbohydrate metabolism from the liver and brain, were evaluated. In chronic caloric restriction, behavioral tests (open-field test and home-cage behavior) were performed. Our results indicate that under acute deprivation, the liver mass and triglyceride content remained unchanged in individuals subjected to prenatal restriction, in contrast to the reduction experienced by the control group. The latter is associated with the expression of the key genes involved in energy homeostasis (Pepck, Pparα/Pparγ), indicating a differential use of nutritional resources. In addition, thrifty animals, subjected to chronic caloric restriction, showed a severe reduction in locomotor and gluconeogenic activity, which is consistent with the regulatory role of Sirt1 and its downstream targets Mao and Pepck. Our results reveal that prenatal caloric restriction translates into a sparing metabolism in response to acute and chronic lack of food in adulthood.
不利的产前营养条件导致的胎儿代谢编程会导致一种称为“节俭表型”的疾病的发生，这种疾病与成年期的糖尿病和肥胖等病理学有关。然而，从生态生理学的角度来看，很少有研究从能量的角度来探讨节俭表型的发展。这可能代表了一种对成年后热量不足条件的适应性优势。本研究的目的是通过在经历不同时间背景下不同饮食条件的啮齿动物模型中进行产前编程来研究节俭表型表达的潜在适应价值。为了填补这一空白，我们分析了来自两个母体妊娠组的成年雄性 Mus musculus（BALB/C）：对照组（随意喂养）和从妊娠第 10 天开始的热量限制组（70%限制）。这些组的成年后代进一步分为两个实验：急性食物剥夺和 60%的慢性热量限制。急性食物剥夺持续 24、48 或 72 小时，而热量限制持续 20 天。对于每个实验，我们评估了与肝脏和大脑中的脂质和碳水化合物代谢相关的形态学变量，如体重和器官质量，以及基因表达。在慢性热量限制中，进行了行为测试（旷场测试和笼内行为）。我们的结果表明，在急性剥夺下，与对照组相比，经历产前限制的个体的肝脏质量和甘油三酯含量保持不变。后者与能量稳态相关的关键基因（Pepck、Pparα/Pparγ）的表达有关，表明对营养资源的不同利用。此外，经历慢性热量限制的节俭动物表现出严重的运动和糖异生活性降低，这与 Sirt1 及其下游靶标 Mao 和 Pepck 的调节作用一致。我们的结果表明，产前热量限制会导致成年期急性和慢性食物缺乏时的代谢节省。
