Desai M, Byrne C D, Meeran K, Martenz N D, Bloom S R, Hales C N
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, United Kingdom.
Am J Physiol. 1997 Oct;273(4):G899-904. doi: 10.1152/ajpgi.1997.273.4.G899.
We have hypothesized that permanent changes caused by poor growth during early development due to maternal malnutrition may be exacerbated by overnutrition of offspring in later life. To test this hypothesis, rats were exposed to a maternal 20% protein diet or an isocaloric 8% protein diet during fetal and postnatal life. All offspring were weaned onto laboratory chow. At 6 wk, rats were fed laboratory chow or a highly palatable diet (high fat and high calorie with adequate protein) and studied at 12 wk after a 48-h fast. The highly palatable diet resulted in excess weight gain and higher plasma insulin levels in all animals. Plasma insulin concentrations were significantly increased in male offspring of dams fed a reduced-protein diet compared with male offspring of dams fed an adequate-protein diet, but no differences were observed between the female offspring. The key hepatic enzymes of glucose homeostasis programmed in offspring of protein-restricted rat dams retained the ability to respond to overnutrition during adult life. In these offspring, however, the enzymes were regulated around a "set point" that was different from that in the controls.
我们已经提出假设，即母亲营养不良导致早期发育期间生长不良所引起的永久性变化，可能会在后代成年后因营养过剩而加剧。为了验证这一假设，在胎儿期和出生后，将大鼠暴露于含20%蛋白质的母体饮食或等热量的8%蛋白质饮食中。所有后代均断奶后喂食实验室饲料。6周时，给大鼠喂食实验室饲料或高适口性饮食（高脂肪、高热量且蛋白质充足），并在禁食48小时后的12周进行研究。高适口性饮食导致所有动物体重过度增加和血浆胰岛素水平升高。与喂食蛋白质充足饮食的母鼠所生雄性后代相比，喂食低蛋白饮食的母鼠所生雄性后代的血浆胰岛素浓度显著升高，但雌性后代之间未观察到差异。蛋白质限制的大鼠母鼠所产后代中，葡萄糖稳态的关键肝酶在成年期仍保留对营养过剩作出反应的能力。然而，在这些后代中，这些酶是围绕一个与对照组不同的“设定点”进行调节的。
