The effects of cafeteria diet feeding on maternal adaptation to pregnancy, growth and development of fetus and glucose homeostasis later in life

Both epidemiological and experimental studies have demonstrated adverse effects of maternal obesity upon both maternal and fetal health. It has been shown that feeding a cafeteria diet in rat pregnancy can induce altered food preferences and greater weight gain in the resulting offspring. This study firstly aimed to examine the effect of diet-induced obesity, or high fat feeding on maternal adaptation to pregnancy and fetal growth. Forty-eight 3-weekold virgin female Wistar rats were randomly divided into two groups fed control (n=24) and cafeteria diet (n=23). 8 weeks later, all rats were mated and after confirming pregnancy half of the rats fed cafeteria diet switched to control, and half of the control rats switched to the cafeteria diet. Maternal cafeteria diet feeding prior to pregnancy resulted in profound adiposity, but did not compromise physiological adaptation to pregnancy or impact upon reproductive success. Maternal cafeteria diet feeding during pregnancy only or maternal obesity induced distinct effects on fetal growth, with pregestational obesity resulting in reduced fetal weight at 20 days gestation. In contrast, cafeteria diet feeding during pregnancy only resulted in increased fetal weight. The main focus of the study was the development of the fetus, and consideration of whether maternal obesity, or cafeteria diet feeding during pregnancy determined body weight, body composition, metabolic biomarkers and glucose homeostasis throughout life. With respect to this point, the same study design was used with additional nutritional challenges during lactation and post-weaning. In contrast to the literature, offspring exposed to cafeteria diet at any stage pre-weaning, showed no evidence of hyperphagia or increased adiposity. Adult offspring exposed to cafeteria diet in early life and weaned onto chow diet, had low fasting glucose and insulin concentrations and were more sensitive to insulin during an i.p. glucose tolerance test. When weaned onto cafeteria diet, offspring exhibited glucose intolerance. There was evidence that rats arrived at a glucose intolerant state via different mechanistic routes which were dependent on the feeding regime during lactation. The data suggested that components of the insulin signalling pathway may be targets for programming by maternal obesity, but that IRS2 and Akt2 do not play major roles. There was also evidence of pancreatic insufficiency in some groups of animals that were fed cafeteria diet during lactation. The observations in this study confirm that maternal over-nutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. The effects on glucose homeostasis were independent of offspring adiposity. However the programming of a glucose intolerant phenotype was dependent upon consumption of cafeteria diet during the post-weaning period