Stimuli or insults during the perinatal period can have lifetime consequences and this long-term effect is called ‘programming’. Early nutrition is an important environmental signal that can induce lifetime effects on metabolism, growth and neurodevelopment and on major disease processes such as hypertension, diabetes, and obesity(Reference Eriksson, Forsen, Tuomilehto, Osmond and Barker1–Reference Lucas, Fewtrell and Cole3). For instance, exclusive breast-feeding is an early environmental stimulus that is known to influence the development of insulin resistance, obesity, hypertension and type 2 diabetes mellitus in later life(Reference Ravelli, van der Meulen, Osmond, Barker and Bleker4–Reference von Kries, Koletzko, Sauerwald, von Mutius, Barnert, Grunert and von Voss6). In this context, the results of the study published recently in the British Journal of Nutrition by Bayol et al. (Reference Bayol, Farrington and Stickland7) are interesting.
Appetite is controlled by appetite-stimulating neuropeptide Y (NPY) and agouti-related peptide (AgRP), and the appetite-inhibitory molecules pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) which regulate energy balance(Reference McMillen, Adam and Muhlhausler8). Hypothalamic appetite regulatory centres develop during the perinatal period(Reference Eriksson, Forsen, Tuomilehto, Osmond and Barker1). Hence, factors that influence brain growth and development will have substantial impact on the development of appetite regulatory centres that, in turn, determine food intake in later life. For instance, postnatal over-nutrition in rats leads to increased early weight gain and fat deposition, hyperphagia, obesity, hyperleptinaemia, hyperglycaemia, hyperinsulinaemia and insulin resistance and the over-fed rats show decreased mean areas of neuronal nuclei and cytoplasm within the paraventricular (PVN), ventromedial (VMN), and arcuate (ARC) nuclei of the hypothalamus and a significant increase in the number of NPY-containing neurons within the ARC and decreased immunostaining for both POMC and α-melanocyte-stimulating hormone(Reference Davidowa, Li and Plagemann9, Reference Fahrenkrog, Harder, Stolaczyk, Melchior, Franke, Dudenhausen and Plagemann10). Furthermore, neuropeptides NPY, AgRP, POMC and CART showed significant changes in their concentrations in the various regions of the hypothalamic nuclei in sheep in response to intrafetal infusion of glucose between 130 and 140 days of gestation(Reference Muhlhausler, Adam, Marracco, Findlay, Roberts, McFarlane, Kauter and McMillen11). These results indicate that neuropeptides which regulate appetite centres and their responses to stimuli such as glucose, insulin and other stimuli are ‘programmed’ in the fetal and perinatal stages of development. This could explain why a maternal junk-food diet in pregnancy and lactation promoted an exacerbated taste for similar food and greater propensity for obesity in rat offspring(Reference Bayol, Farrington and Stickland7). Maternal junk-food intake programmed the offspring hypothalamus to crave for junk food.
The brain is rich in PUFA especially arachidonic acid (AA) and DHA which constitute as much as 30 to 50 % of the total fatty acids in the brain, where they are predominantly associated with membrane phospholipids. These PUFA activate syntaxin 3, a plasma membrane protein that has an important role in the growth of neurites(Reference Darios and Davletov12). Junk food is known to be energy-dense and rich in saturated and trans fatty acids that could interfere with the metabolism of essential fatty acids(Reference Das13) and so could potentially lead to PUFA deficiency in the mother and offspring during the critical period of brain growth, development and maturation leading to inappropriate synaptic connections of hypothalamic neurons. This may lead to the hypothalamic ‘body weight–appetite–satiety set point’ set such that it promotes an exacerbated taste for similar food and greater propensity for obesity in rat offspring. If this proposal is true, it implies that provision of PUFA during the critical perinatal period of growth would prevent the development of obesity and metabolic syndrome X.