Nutritional programming, regulation and some ways for prevention/treatment to ameliorate or normalize adverse outcomes of programming are discussed. Epidemiological studies in human and animal experiments showed that nutrition during fetal and neonatal life may lead to related disorders in adulthood. But several argues may question its validity arising the question of the adequate models used to reproduce human situations. Protein level in milk formula intake by infant during neonatal life is discussed. Body weight at birth reflects the product growth trajectory during fetal life. Low birth weight is considered as the result of an adverse growth trajectory and is often associated with later metabolic diseases in adult age. But, the sum of prenatal growth trajectory, rapid growth in early infancy (catch up growth), early adiposity rebound in childhood must be considered to determine the origins of later diseases in adulthood. The review focuses the regulation of nutritional imprinting on hormonal and epigenetic mechanisms which are complementary. The HPA axis and GH-IGF axis may have a crucial role in the regulation induced by nutritional programming. The persistent alterations seem to be a consequence, at least in part, of elevated insulin levels during ‘critical periods” of pre- and early postnatal development. Also, leptin seems to play an important role in this complex system. New knowledge about these mechanisms involved suggest the development of new, rational, and effective preventive and/or therapeutic options before and/or after birth. Thus, early infancy may provide an opportunity for intervention aimed at reducing later disease risk.

/pdf/adverse-effects-of-nutritional-programming-during-prenatal-4vu5kv21im.pdf

Adverse effects of nutritional programming during prenatal and early postnatal life, some aspects of regulation and potential prevention and treatments.

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S2040174416000477

A review of fundamental principles for animal models of DOHaD research: An Australian perspective

The acute phase response is the immediate host response to infection, inflammation and trauma and can be monitored by measuring the acute phase proteins (APP) such as haptoglobin (Hp) or serum amyloid A (SAA). The plane of nutrition during pregnancy is known to affect many mechanisms including the neuroendocrine and neuroimmune systems in neonatal animals but effects on the APP are unknown. To investigate this phenomenon the serum concentration of Hp and SAA was initially determined in non-stimulated lambs from 3 groups (n = 10/group). The dams of the lambs of the respective groups were fed 100% of requirements throughout gestation (High/High; HH); 100% of requirements for the first 65 d of gestation followed by 70% of requirements until 125 d from when they were fed 100% of requirements (High/Low; HL); 65% of liveweight maintenance requirements for the first 65 d gestation followed by 100% of requirements for the remainder of pregnancy (Low/High; LH). The dynamic APP response in the lambs was estimated by measuring the concentration of Hp and SAA following routine vaccination with a multivalent clostridial vaccine with a Pasteurella component, Heptavac P™ following primary and secondary vaccination. The Hp and SAA concentrations were significantly lower at the time of vaccination (day 8–14) than on the day of birth. Vaccination stimulated the acute phase response in lambs with increases found in both Hp and SAA. Maternal undernutrition led to the SAA response to vaccination being significantly lower in the HL group than in the HH group. The LH group did not differ significantly from either the HH or HL groups. No significant effects of maternal undernutrition were found on the Hp concentrations. A significant reduction was found in all groups in the response of SAA following the second vaccination compared to the response after the primary vaccination but no change occurred in the Hp response. Decreased SAA concentrations, post-vaccination, in lambs born to ewes on the HL diet shows that maternal undernutrition prior to parturition affects the innate immune system of the offspring. The differences in response of Hp and SAA to primary and secondary vaccinations indicate that the cytokine driven APP response mechanisms vary with individual APP.

/pdf/maternal-undernutrition-and-the-ovine-acute-phase-response-24cvledyqe.pdf

Maternal undernutrition and the ovine acute phase response to vaccination

Nutrient intake in the bovine during early and mid-gestation causes sex-specific changes in progeny plasma IGF-I, liveweight, height and carcass traits

https://www.kidney-international.org/article/S0085-2538(15)52633-1/pdf

Hypertension and impaired renal function accompany juvenile obesity: the effect of prenatal diet.

The liver is a major metabolic and endocrine organ of critical importance in the regulation of growth and metabolism. Its function is determined by a complex interaction of nutritionally regulated counter-regulatory hormones. The extent to which hepatic endocrine sensitivity can be programed in utero and whether the resultant adaptations persist into adulthood is unknown and was therefore the subject of this study. Young adult male sheep born to mothers that were fed either a control diet (i.e.100% of total live weight-maintenance requirements) throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0 to 95 days gestation and thereafter 100% of requirements (taking into account increasing fetal mass) were entered into the study. All mothers gave birth normally at term, the singleton offspring were weaned at 16 weeks, and then reared at pasture until 3 years of age when their livers were sampled. NR offspring were of similar birth and body weights at 3 years of age when they had disproportionately smaller livers than controls. The abundance of mRNA for GH, prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the abundance of the mitochondrial protein voltage-dependent anion channel and the pro-apoptotic factor Bax were up regulated relative to controls. In conclusion, maternal nutrient restriction in early gestation results in adult offspring with smaller livers. This may be mediated by alterations in both hepatic mitogenic and apoptotic factors.

/pdf/maternal-nutrient-restriction-in-early-pregnancy-programs-4emxmubt5s.pdf

C Jones

Papers

Maternal nutrient restriction in early pregnancy programs hepatic mRNA expression of growth-related genes and liver size in adult male sheep.