Prenatal exposure to undernutrition and programming of responses to high-fat feeding in the rat.

Fetal undernutrition programmes risk of later metabolic disorders. Postnatal factors modify the programmed phenotype. This study aimed to assess the effects of a postnatal high-fat (HF) challenge on body weight gain, adiposity and gene expression following prenatal undernutrition. Pregnant rats were fed either a control diet or a low-protein (LP) diet, targeted at days 0-7 (LPE), days 8-14 (LPM), or days 15-22 (LPL) gestation. At 12 weeks of age offspring were either fed standard laboratory chow diet (4.13 % fat), or a 39.5 % fat diet, for 10 weeks. LP exposure had no effect on weight gain or abdominal fat in males. Females exposed to LP diet in utero exhibited a similar weight gain on HF diet as on the chow diet. Programming of fat deposition was noted in LPE females and males of the LPM and LPL groups (P = 0.019). Hypothalamic expression of galanin mRNA was similar in all groups, but expression of the galanin-2 receptor was modified by LP exposure in female offspring. Hepatic expression of sterol response element binding protein (SREBP-1c) was decreased by LP at both the mRNA (P = 0.008) and protein (P < 0.001) level. HF feeding increased expression of SREBP-1c mRNA three-fold in controls, with little response noted in the LP groups. Interactions of factors such as postnatal diet, age and sex act together with prenatal factors to determine metabolic function and responsiveness at any stage of postnatal life. This study further establishes a role for prenatal nutrition in programming the genes involved in lipid metabolism and appetite regulation.

Fetal programming of appetite by exposure to a maternal low-protein diet in the rat.

Undernutrition in fetal life programmes risk of obesity and the metabolic syndrome in adult life. Rat studies indicate that exposure to a maternal low-protein diet throughout fetal life establishes a preference for high-fat foods. The present study aimed to assess the effect of low protein exposure during discrete 7-day periods of gestation upon feeding behaviour (full gestation 22 days). Pregnant rats were fed control or low-protein diet, with low-protein feeding targeted at day 0--7 (LP Early), day 8--14 (LP Mid) or day 15--22 (LP Late) of gestation. At 12 weeks of age, offspring were placed on a macronutrient self-selection regimen. Prenatal protein restriction programmed feeding behaviour in female, but not male, offspring. Among females, all low-protein exposed groups consumed less fat than the control group (P<0.05). Male offspring showed no changes in feeding behaviour. In males and females fed a low-fat chow diet, there were metabolic differences between the groups. LP Early and LP Late males had greater hepatic glycogen stores than control animals. There were no differences in the size of abdominal fat depots in either male or female rats exposed to low-protein diet at any point in gestation. The data suggest that programming of feeding behaviour is likely to be gender-specific and dependent upon the timing of nutrient insult in fetal life. This work may have implications for the development of the metabolic syndrome.

Animal models of programming: early life influences on appetite and feeding behaviour.

Epidemiological observations of associations between early life nutrition and long-term disease risk have prompted detailed experimental investigation of the biological basis of programming. Studies using rodent or large animal models have clearly established the biological plausibility of nutritional programming and are now yielding important information on underlying mechanisms. Nutritional interventions in pregnancy, including global food restriction, protein restriction, micronutrient restriction and excess fat feeding, determine a consistent cluster of disorders in the resulting offspring. The common association of such diverse nutritional disturbances with hypertension, glucose intolerance and adiposity suggests that a small number of simple common mechanisms are active in response to fetal nutrient imbalance. Studies of rodent models indicate that fetal undernutrition determines adult adiposity. It is unclear whether the increase in central adiposity is related to increased food intake or reduced energy expenditure, although evidence exists to suggest that both may act together. Rats subject to intrauterine protein restriction exhibit increased preference for high fat foods. Feeding of energy dense foods to rats that were undernourished in utero promotes a greater degree of obesity than is noted in animals subject to adequate nutrition in fetal life. There is evidence to suggest that programming of appetite may stem from remodelling of hypothalamic structures that control feeding and programming of the expression of genes involved in responses to orexogenic hormones. The early life programming of appetite and obesity is a complex phenomenon and our understanding of how maternal nutrition determines later energy balance is at a very early stage.

Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat.

Nutrient restriction in pregnancy has been shown to programme adult obesity. Modulation of feeding behaviour may provide a mechanism through which obesity may be programmed. Pregnant Wistar rats were fed either a control diet or a low-protein (LP) diet throughout gestation. Their offspring were allocated to a self-selected-diet protocol to assess appetite and food preferences at 12 and at 30 weeks of age. Self-selection of high-fat, high-protein or high-carbohydrate foods by 12-week-old rats indicated that the prenatal environment influenced feeding behaviour. Both male and female offspring of LP-fed mothers consumed significantly more of the high-fat (P<0.001) and significantly less (P<0.02) of the high-carbohydrate food than the control animals. Female, but not male, offspring of LP-fed rats failed to adjust food intake to maintain a constant energy intake and had higher fat (P<0.005) and energy intakes (P<0.05) than control female rats. At 30 weeks of age there were no differences in the pattern of food selection between the two groups of animals. Male offspring of LP-fed rats had significantly more gonadal fat than control animals (P<0.05), but analysis of total body fat content indicated that there was no significant difference in overall adiposity. The present study suggests that in young adults at least, early life exposure to undernutrition determines a preference for fatty foods. Maternal nutrition may thus promote changes in systems that are involved in control of appetite or the perception of palatability.