Early programming of weight gain in mice prevents the induction of obesity by a highly palatable diet

Abstract

Poor early growth is associated with Type II diabetes, hypertension and other features of the metabolic syndrome in adulthood. It has been suggested that this results from the development of a thrifty phenotype by a malnourished fetus. Such a phenotype would predispose the offspring to the development of obesity if born into conditions of over-nutrition. The present study aimed to determine if early nutrition affected subsequent development of obesity. Mice were established as follows: (a) controls (offspring of control dams), (b) recuperated (offspring of dams fed a low-protein diet during pregnancy, but nursed by control dams) and (c) postnatal low-protein (offspring of control dams nursed by low-protein-fed dams). Mice were weaned on to standard laboratory chow or a cafeteria diet. Recuperated offspring, although smaller at birth ( P <0.01), caught up and exceeded the weight of control offspring by 7 days of age ( P <0.001). Postnatal low-protein offspring were smaller than controls by 7 days of age ( P <0.001). Recuperated animals gained more weight than controls when given free access to a highly palatable diet ( P <0.01). Postnatal low-protein animals showed no additional weight gain when given a highly palatable diet compared with chow-fed litter-mates. These results suggest that the early environment has long-term consequences for weight gain. These programmed responses are powerful enough to block excess weight gain from a highly palatable diet and, thus, have major implications for the drug-free regulation of food intake and obesity.

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

“…This is in direct contrast to the studies of Vickers et al 14,26 Although ageing brought out some subtle differences in the amount of fat relative to body weight and the distribution of fat between subcutaneous and abdominal sites, the data favour the view that undernutrition in fetal life does not programme obesity, consistent with the findings in mice. 28 However, as shown by other studies, this is a situation that may change if the animals were challenged with a high fat diet in postnatal life. 23,24 In humans, the data relating to programming of obesity is also somewhat inconclusive.…”

“…27 In contrast, studies of mice exposed to LP diets in utero show no evidence of an increased propensity to become obese when fed a high fat diet. 28 The aim of the present paper was to consider the impact of prenatal protein restriction upon the deposition of fat, appetite and locomotor activity of ageing rats. Most previous studies of nutritional programming have tended to focus on young adult animals, so consideration of longer term effects is an important aspect of this work.…”

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition: a protective effect?

“…However, despite this period of increased growth, early undernourished rats fed a CD had a similar increase in body weight compared with control. The timing of the growth restriction appears critical as previous studies indicate that growth restriction during gestation followed by catch-up growth during suckling can increase the risk of obesity in rodents, 30,42 whereas normal gestation but restricted nutrition during suckling reduces the risk of obesity. 6,7,42 From the current study, it is clear that growth restriction during the suckling period of rodents leads to long-term decreases in body weight when fed low-fat chow diet into adulthood.…”

High-protein diet during gestation and lactation affects mammary gland mRNA abundance, milk composition and pre-weaning litter growth in mice

“…low protein, restricted energy intake) on pregnancy outcome in humans (Godfrey et al, 1996) and animals (Ozanne et al, 2004;Rees et al, 2006;Fagundes et al, 2007). High-protein (HP) diets have been shown to cause weight loss by inducing longer postprandial satiety and increase dietary thermogenesis that led to a lower subsequent energy intake (Johnston et al, 2002;Halton and Hu, 2004).…”