ABSTRACT
The thrifty phenotype hypothesis has provided a conceptual framework that can be tested using animal models to investigate mechanisms behind the observations in humans that fetal growth restriction is associated with the future development of diabetes and the metabolic syndrome. The most widely studied model involves looking at offspring of rat dams who were protein restricted during pregnancy (and sometimes lactation). Offspring from such pregnancies are growth restricted at birth. In young adult life, male offspring tend to have increased whole body sensitivity to insulin, along with good glucose tolerance. Parallel with this, a number of tissues including liver, skeletal muscle and adipocytes have increased insulin receptor expression. As the animals age, however, the low protein offspring undergo a metabolic shift such that they become hyperglycaemic and hyperinsulinaemic. If the protein-reduced diet is supplemented with methionine, the offspring show consistently raised blood pressures. In one study, effects associated with both dietary-induced obesity and early protein restriction were linked (in an additive fashion) to hypertension in female rats. The maternal low protein rat model is therefore able to reproduce many of the findings observed in humans which are linked with restricted fetal growth.
