Vitamin D3 (Vit D3) and 25(OH)D3 are used as dietary sources of active vitamin D (1,25(OH)2D3) in pig husbandry. Although acting primarily on intestine, kidney and bone, their use in pig nutrition has shown a wide range of effects also in peripheral tissues. However, there is an ambiguity in the existing literature about whether the effects of Vit D3 and 25(OH)D3 differ in attributing the molecular and phenotypic outcomes in pigs. We searched Web of Science and PubMed databases concerning the efficacy of Vit D3 in comparison with 25(OH)D3 on pig physiology, i.e. reproductive capacities, growth performance, immunity and bone development. Dietary intake of Vit D3 or 25(OH)D3 did not influence the reproductive capacity of sows. Unlike Vit D3, the maternal intake of 25(OH)D3 significantly improved the growth performance of piglets, which might be attributed to maternally induced micronutrient efficiency. Consequently, even in the absence of maternal vitamin D supplementation, 25(OH)D3-fed offspring also demonstrated better growth than the offspring received Vit D3. Moreover, a similar superior impact of 25(OH)D3 was seen with respect to serum markers of innate and humoral immunity. Last but not least, supplements containing 25(OH)D3 were found to be more effective than Vit D3 to improve bone mineralisation and formation, especially in pigs receiving basal diets low in Ca and phosphorus. The insights are of particular value in determining the principal dietary source of vitamin D to achieve its optimum utilisation efficiency, nutritional benefits and therapeutic potency and to further improve animal welfare across different management types.

The nutritional status experienced in the early development of life plays a vital role in the long-term metabolic state of the individual, which is known as nutritional programming. The present study investigated the long-term effects of vegetable oil (VO) nutritional programming during the early life of large yellow croaker. First, larvae were fed either a fish oil (FO) diet or a VO diet for 30 d. Subsequently, under the same conditions, all fish were fed a commercial diet for 90 d and thereafter challenged with an FO or VO diet for 30 d. The results showed that growth performance was significantly lower in larvae fed the VO diet than in those in fed the FO diet in the stimulus phase. Notably, VO nutritional history fish showed lower levels of liver lipids liver total triglycerides and serum nonesterified free fatty acids than the FO nutritional history fish when juveniles were challenged with the VO diet, which was consistent with the expression of lipogenesis-related genes and proteins. Moreover, the VO nutritional history fish showed lower liver damage and higher antioxidant capacity than FO nutritional history fish when challenged with the VO diet. In summary, this study showed that a short VO stimulus during the early life stage of large yellow croaker, had a long-term effect on lipid metabolism and the antioxidant system. Specifically, VO nutritional programming had a positive effect on alleviating abnormal lipid deposition on the liver, liver damage, and the reduction of hepatic antioxidant capacity caused by a VO diet.

This study evaluated how different forms of selenium (Se) supplementation into rainbow trout broodstock diets modified the one-carbon metabolism of the progeny after the beginning of exogenous feeding and followed by hypoxia challenge. The progeny of three groups of rainbow trout broodstock fed either a control diet (Se level: 0·3 µg/g) or a diet supplemented with inorganic sodium selenite (Se level: 0·6 µg/g) or organic hydroxy-selenomethionine (Se level: 0·6 µg/g) was cross-fed with diets of similar Se composition for 11 weeks. Offspring were sampled either before or after being subjected to an acute hypoxic stress (1·7 mg/l dissolved oxygen) for 30 min. In normoxic fry, parental Se supplementation allowed higher glutathione levels compared with fry originating from parents fed the control diet. Parental hydroxy-selenomethionine treatment also increased cysteine and cysteinyl–glycine concentrations in fry. Dietary Se supplementation decreased glutamate–cysteine ligase (cgl) mRNA levels. Hydroxy-selenomethionine feeding also lowered the levels of some essential free amino acids in muscle tissue. Supplementation of organic Se to parents and fry reduced betaine-homocysteine S-methyltransferase (bhmt) expression in fry. The hypoxic stress decreased whole-body homocysteine, cysteine, cysteinyl-glycine and glutathione levels. Together with the higher mRNA levels of cystathionine beta-synthase (cbs), a transsulphuration enzyme, this suggests that under hypoxia, glutathione synthesis through transsulphuration might have been impaired by depletion of a glutathione precursor. In stressed fry, S-adenosylmethionine levels were significantly decreased, but S-adenosylhomocysteine remained stable. Decreased bhmt and adenosylmethionine decarboxylase 1a (amd1a) mRNA levels in stressed fry suggest a nutritional programming by parental Se also on methionine metabolism of rainbow trout.

Early nutrition may have long-lasting metabolic impacts in adulthood. Even though breast milk is the gold standard, most infants are at least partly formula-fed. Despite obvious improvements, infant formulas remain perfectible to reduce the gap between breastfed and formula-fed infants. Improvements such as reducing the protein content, modulating the lipid matrix and adding prebiotics, probiotics and synbiotics, are discussed regarding metabolic health. Numerous questions remain to be answered on how impacting the infant formula composition may modulate the host metabolism and exert long-term benefits. Interactions between early nutrition (composition of human milk and infant formula) and the gut microbiota profile, as well as mechanisms connecting gut microbiota to metabolic health, are highlighted. Gut microbiota stands as a key actor in the nutritional programming but additional well-designed longitudinal human studies are needed.

The present study investigated nutritional programming in Atlantic salmon to improve utilisation of a vegetable-based diet. At first exogenous feeding, fry were fed either a marine-based diet (Diet Mstimulus, 80% fishmeal (FM)/4% fish oil (FO)) or a vegetable-based diet (Diet Vstimulus, 10% FM/0% FO) for 3 weeks. Subsequently, all fish were then fed under the same conditions with a commercial, marine-based, diet for 15 weeks and thereafter challenged with a second V diet (Diet Vchallenge, 10% FM/0% FO) for 6 weeks. Diploid and triploid siblings were run in parallel to examine ploidy effects. Growth performance, feed intake, nutrient utilisation and intestinal morphology were monitored. Fish initially given Diet Vstimulus (V-fish) showed 24 % higher growth rate and 23 % better feed efficiency compared with M-fish when later challenged with Diet Vchallenge. There was no difference in feed intake between nutritional histories, but increased nutrient retentions highlighted the improved utilisation of a V diet in V-fish. There were generally few significant effects of nutritional history or ploidy on enteritis scores in the distal intestine after the challenge phase as only V-triploids showed a significant increase (P<0·05) in total score. The data highlighted that the positive effects were most likely a result of nutritional programming and the ability to respond better when challenged later in life may be attributed to physiological and/or metabolic changes induced by the stimulus. This novel study showed the potential of nutritional programming to improve the use of plant raw material ingredients in feeds for Atlantic salmon.

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 m) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP–6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [14C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [14C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.

There is increasing evidence that hyperenergetic diets have an impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western-type diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a CD and exposed both male and female offspring to a novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a training/familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial. The choice trial was performed following inter-trial interval (ITI) delays of up to 4 h. Maternal diet did not have an impact on exploration of the objects by either sex during the familiarisation trial. Control males discriminated the novel from the familiar object, indicating intact memory with an ITI of 1 h, but not 2 or 4 h. The CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2 h ITI. In contrast, control females exhibited discrimination following both 1 and 2 h ITI, but the CD impaired performance. In summary, the present study shows that maternal exposure to the CD programmes NOD in the adult. In better-performing females, dietary programming interferes with NOD, whereas NOD was improved in males after lactational CD feeding.

Exposure to a maternal junk food (JF) diet in utero and during the suckling period has been demonstrated to increase the preference for palatable food and increase the susceptibility to diet-induced obesity in adult offspring. We aimed to determine whether the effects of prenatal exposure to JF could be ameliorated by cross-fostering offspring onto dams consuming a standard rodent chow during the suckling period. We report here that when all offspring were given free access to the JF diet for 7 weeks from 10 weeks of age, male offspring of control (C) or JF dams that were cross-fostered at birth onto JF dams (C-JF, JF-JF), exhibited higher fat (C-C: 12.3 ± 0.34 g/kg/day; C-JF: 14.7 ± 1.04 g/kg/day; JF-C: 11.5 ± 0.41 g/kg/day; JF-JF: 14.0 ± 0.44 g/kg/day; P < 0.05) and overall energy intake (C-C: 930.1 ± 18.56 kJ/kg/day; C-JF: 1029.0 ± 82.9 kJ/kg/day; JF-C: 878.3 ± 19.5 kJ/kg/day; JF-JF: 1003.4 ± 25.97 kJ/kg/day; P < 0.05) than offspring exposed to the JF diet only before birth (JF-C) or not at all (C-C). Female offspring suckled by JF dams, despite no differences in food intake, had increased fat mass as percentage of body weight (C-C: 19.9 ± 1.33%; C-JF: 22.8 ± 1.57%; JF-C: 17.4 ± 1.03%; JF-JF: 22.0 ± 1.0%; P < 0.05) after 3 weeks on the JF diet. No difference in fat mass was observed in male offspring. These findings suggest that the effects of prenatal exposure to a JF diet on food preferences in females and susceptibility to diet-induced obesity in males can be prevented by improved nutrition during the suckling period.

Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis® (Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARγ, CCAAT/enhancer-binding protein and retinoid X receptor α in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

Exposure to isoflavones (ISO), abundant in soy protein infant formula, for the first 5 days of life results in higher bone mineral density (BMD), greater trabecular connectivity and higher peak load of lumbar vertebrae (LV) at adulthood. The effect of lengthening the duration of exposure to ISO on bone development has not been studied. This study determined if providing ISO for the first 21 days of life, which more closely mimics the duration that infants are fed soy protein formula, results in higher BMD, improved bone structure and greater strength in femurs and LV than a 5-day protocol. Female CD-1 mice were randomized to subcutaneous injections of ISO (7 mg/kg body weight/day) or corn oil from postnatal day 1 to 21. BMD, structure and strength were measured at the femur and LV at 4 months of age, representing young adulthood. At the LV, exposure to ISO resulted in higher (P < 0.05) BMD, trabecular connectivity and peak load compared with control (CON). Exposure to ISO also resulted in higher (P < 0.05) whole femur BMD, higher (P < 0.05) bone volume/total volume and lower (P < 0.05) trabecular separation at the femur neck, as well as greater (P < 0.05) peak load at femur midpoint and femur neck compared with the CON group. Exposure to ISO throughout suckling has favorable effects on LV outcomes, and, unlike previous studies using 5-day exposure to ISO, femur outcomes are also improved. Duration of exposure should be considered when using the CD-1 mouse to model the effect of early life exposure of infants to ISO.

Early postnatal nutrition is involved in metabolic programming, an excess of protein being suspected to enhance early growth and the propensity to later develop insulin resistance and type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that excessive protein intake during the suckling period would overstimulate the endocrine pancreas in the short term and alter durably its maturation, contributing to the later disruption of glucose homeostasis. Normal-birth-weight and low-birth-weight piglets were fed isoenergetic formulae providing an adequate-protein (AP, equivalent to sow milk) or a high-protein (HP, +48 %) supply between 7 and 28 d of age and were fed a standard diet until 70 d of age. During the formula-feeding period, the HP formula did not modify postprandial insulin secretion but transiently increased fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR, P < 0·05). Fasting insulin and HOMA-IR were restored to AP piglets' values 1 month after weaning. The structure of the endocrine pancreas was not affected by the protein content of the formula. The weight at birth had no major effect on the studied parameters. We concluded that a high-protein supply during the suckling period does not interfere with insulin secretion and endocrine pancreas maturation in the short term. It has no consequences either on glucose tolerance 1 month after weaning. The present study demonstrated that up-regulation of postprandial insulin secretion is not involved in higher growth observed in piglets fed a HP formula.

Body composition in children is of increasing interest within the contexts of childhood obesity, clinical management of patients and nutritional programming as a pathway to adult disease. Energy imbalance appears to be common in many disease states; however, body composition is not routinely measured in patients. Traditionally, clinical interest has focused on growth or nutritional status, whereas more recent studies have quantified fat mass and lean mass. The human body changes in proportions and chemical composition during childhood and adolescence. Most of the weight gain comprises lean mass rather than fat. In general, interest has focused on percentage fat, and less attention has been paid to the way in which lean mass varies within and between individuals. In the general population secular trends in BMI have been widely reported, indicating increasing levels of childhood obesity, which have been linked to reduced physical activity. However, lower activity levels may potentially lead not only to increased fatness, but also to reduced lean mass. This issue merits further investigation. Diseases have multiple effects on body composition and may influence fat-free mass and/or fat mass. In some diseases both components change in the same direction, whereas in other diseases, the changes are contradictory and may be concealed by relatively normal weight. Improved techniques are required for clinical evaluations. Both higher fatness and reduced lean mass may represent pathways to an increased risk of adult disease.

Leptin is a 16 kDa protein synthesized and secreted primarily from adipocytes. Leptin acts centrally to regulate appetite and energy expenditure and has peripheral effects to coordinate whole-body energy metabolism. Leptin acts as an energy balance and nutrient sensor; its expression and function are regulated by endocrine and dietary factors. Leptin regulates lipid metabolism, specifically lipid storage in adipocytes as well as in skeletal muscle, liver and the pancreas. Effects of leptin on tissue lipid metabolism include regulation of lipogenesis and fatty acid oxidation. Leptin resistance is a hallmark of rodent and human obesity and appears to be due to defects in leptin-receptor signalling (proximal and perhaps distal) as well as impaired leptin transport into the brain. Dietary composition, especially dietary fatty acid intake and profile, impacts on the expression of genes encoding leptin and leptin receptors as well as downstream leptin effectors. Dietary fat consumption, especially consumption of saturated fatty acids, can induce leptin resistance. Leptin has been implicated in nutritional programming during fetal and neonatal growth with long-term effects on susceptibility to obesity, diabetes and CHD in adults.

There is now compelling evidence that growth patterns in early life are associated with risk of the metabolic syndrome in adulthood, although the relative importance of prenatal v. postnatal growth for such associations remains controversial. Body composition may play a key role in the ‘programming’ of such diseases, through itself being programmed by early growth, and perhaps also by being a mediator of the programming process. Early studies reporting positive associations between birth weight and adult BMI suggested a tendency for large babies to become obese adults. Such findings appeared contradictory to the many studies linking low birth weight with increased risk of the metabolic syndrome. Recent studies now indicate that birth weight is strongly predictive of later lean mass, and has a much weaker association with later fatness. Studies that link low birth weight with a more central adipose distribution in later life remain controversial, and require confirmation using more sophisticated methodologies. Findings for infant growth rate appear population-specific, with infant weight gain predicting subsequent lean mass in developing countries, but predicting subsequent fat mass and obesity in industrialised populations. Further studies are required on this issue, to ensure that appropriate public health policies are recommended for countries across the range of economic development. Although the links between early growth and later disease risk implicate early-life nutrition, either in utero or during infancy, few prospective studies have explored the influence of early diet on later body composition. Many studies have associated breast-feeding with a reduced prevalence of obesity categorised by BMI; however, the few studies directly evaluating childhood fatness provide little support for this hypothesis. Recent advances in the ability to measure body composition during the infant period offer a major opportunity to improve the understanding of the nutritional programming of body composition and its contribution, or lack thereof, to subsequent disease risk.

Fetal growth and development is dependent upon the nutritional, hormonal and metabolic environment provided by the mother. Any disturbance in this environment can modify early fetal development with possible long-term outcomes as demonstrated by extensive work on ‘programming’. Growth restriction resulting from a deficit in tissue/organ cell number (as measured by tissue DNA content) is irrecoverable. However, when the cell size (or cell protein content) is reduced, the effects on growth may not be permanent.

Recent epidemiological studies using archival records of anthropometric measurements related to early growth in humans have shown strong statistical associations between these indices of early development and diseases in later life. It has been hypothesised that the processes explaining these associations involve adaptive changes in fetal organ development in response to maternal and fetal malnutrition. These adaptations may permanently alter adult metabolism in a way which is beneficial to survival under continued conditions of malnutrition but detrimental when nutrition is abundant.

This hypothesis is being tested in a rat model which involves studying the growth and metabolism in the offspring of rat dams fed a low-protein diet during pregnancy and/or lactation. Using this rat model, it has been demonstrated that there is:

(i) Permanent growth retardation in offspring nursed by dams fed a low-protein diet.

(ii) Permanent and selective changes in organ growth. Essential organs like the brain and lungs are relatively protected from reduction in growth at the expense of visceral organs such as the liver, pancreas, muscle and spleen.

(iii) Programming of liver metabolism as reflected by permanent changes in activities of key hepatic enzymes of glycolysis and gluconeogenesis (glucokinase and phosphoenolpyruvate carboxykinase) in a direction which would potentially bias the liver towards a ‘starved’ setting. We have speculated that these changes could be a result of altered periportal and perivenous regions of the liver which may also affect other aspects of hepatic function.

(iv) Deterioration in glucose tolerance with age.

(v) An increase in the life span of offspring exposed to maternal protein restriction only during the lactation period, and a decrease in life span when exposed to maternal protein restriction only during gestation.

These studies show that hepatic metabolism and even longevity can be programmed by events during early life.

Epidemiological studies in humans show that size in early life is related to blood cholesterol concentrations in adult life, raising the hypothesis that early nutrition programs later lipid metabolism, affecting risk for later vascular disease. Here, we tested the hypothesis that nutrition during pregnancy or lactation in the rat programs lipid metabolism in the offspring, studied in adult life (mean 6 months). Rats (n 35) from normally-fed dams (controls) were compared with (1) rats (n 22) from dams protein-restricted in pregnancy and lactation; (2) rats (n 9) born to normally-fed mothers crossed to protein- restricted lactating dams and (3) those (n 9) born of protein-restricted dams and crossed to normally-fed lactating animals. In these latter three groups the offspring showed long-term reduction in plasma cholesterol, HDL-cholesterol and triacylglycerol concentrations compared with controls. The effects were predominantly in males. These findings suggest that in the rat the sensitive period for nutritional programming of cholesterol and triacylglycerol metabolism is both pre- and postnatal (pre-weaning) and that rats may be ‘indirectly’ programmed by altering the maternal nutritional milieu during gestation or lactation. whilst it has been hypothesized that early human undernutrition programs risk for vascular disease, one aspect of undernutrition, low maternal protein intake, in this rat model programmed lower plasma cholesterol and triacylglycerol concentrations.

Recent epidemiological studies in people whose birth weights were recorded many years ago suggest links between impaired growth during early life and the development of diseases, including diabetes, much later in life. The long-term effects of retarded early growth are proposed to result from malnutrition at critical periods of fetal or infant development leading to reduction in the growth of organs and permanent changes in their metabolism or structure, or both. In order to investigate this, a rat model was established which involved feeding either a diet containing 200 g protein/kg or an isoenergetic diet containing 80 g protein/kg to pregnant and lactating rats. In addition, cross-fostering techniques were employed which allowed a separate evaluation of the prenatal or the postnatal periods. The offspring were studied at 21 d of age or were weaned onto a normal laboratory chow and studied at 11 months of age. The 80g protein/kg diet during pregnancy did not affect the overall reproductive performance although more subtle differences were evident. Permanent growth retardation was evident in offspring subjected to maternal protein restriction during the postnatal period. At 21 d of age the offspring of protein-restricted mothers exhibited selective changes in organ growth: compared with the body weight, the lung and brain experienced a smaller decrease in weight; the heart, kidney and thymus decreased proportionately; whereas, the pancreas, spleen, muscle and liver showed a greater reduction in weight. In older animals the muscle weight was lower in the male rats and the relative weight ofpancreas was increased in the female rats.