Early life programming of health and disease: The long-term consequences of obesity in pregnancy

The prevalence of overweight and obesity is rising in all parts of the world and, among young women, it presents a very clear danger during pregnancy. Women who are overweight or who gain excessive weight during pregnancy are at greater risk of complications in pregnancy and labour, and are more likely to lose their child to stillbirth or die themselves during pregnancy. This narrative review considers the evidence that, in addition to increasing risk of poor pregnancy outcomes, obesity has the capacity to programme foetuses to be at greater risk of cardiometabolic disorders later in life. An extensive body of evidence from prospective and retrospective cohorts, as well as record linkage studies, demonstrates associations of maternal obesity and/or gestational diabetes with cardiovascular disease, as well as type 1 and type 2 diabetes. Studies in animals suggest that these associations are underpinned by adaptations that occur in foetal life, which remodel the structures of major organs, including the brain, kidney and pancreas

Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat

Peer reviewedPublisher PD

Body composition and behaviour in adult rats are influenced by maternal diet, maternal age and high-fat feeding

Fetal exposure to maternal undernutrition has lifelong consequences for physiological and metabolic function. Maternal low-protein diet is associated with an age-related phenotype in rats, characterised by a period of resistance to development of obesity in early adulthood, giving way to an obesity-prone, insulin-resistant state in later adulthood. Offspring of rats fed a control (18 % casein) or low-protein (9 % casein; LP) diet in pregnancy were challenged with a high-fat diet at 9 months of age. To assess whether other maternal factors modulated the programming effects of nutrition, offspring were studied from young (2–4 months old) and older (6–9 months old) mothers. Weight gain with a high-fat diet was attenuated in male offspring of older mothers fed LP (interaction of maternal age and diet; P = 0·011) and adipose tissue deposition was lower with LP feeding in both males and females (P < 0·05). Although the resistance to weight gain and adiposity was partially explained by lower energy intake in offspring of LP mothers (P < 0·001 males only), it was apparent that energy expenditure must be influenced by maternal diet and age. Assessment of locomotor activity indicated that energy expenditure associated with physical activity was unlikely to explain resistance to weight gain, but showed that offspring of older mothers were more anxious than thoseof younger mothers, with more rearing observed in a novel environment and on the elevated plus-maze. The data showed that in addition to maternal undernutrition, greater maternal age may influence development and long-term body composition in the rat

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

<p>Abstract</p> <p>Background</p> <p>Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy <it>per se </it>and with compromised plasma volume expansion in rats fed a low-protein diet.</p> <p>Methods</p> <p>Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle.</p> <p>Results</p> <p>As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT₂R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance.</p> <p>Conclusion</p> <p>Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.</p

Setting targets leads to greater long-term weight losses and ‘unrealistic’ targets increase the effect in a large community-based commercial weight management group

Background. Setting personal targets is an important behavioural component in weight management programmes. Normal practice is to encourage ‘realistic’ weight loss but the under-pinning evidence base for this is limited and controversial. This study investigates the effect of number and size of weight loss targets on long-term weight loss in a large community sample of adults. Methods. Weight change, attendance and target weight data for all new UK members, joining January to March 2012 was extracted from a commercial slimming organisation’s electronic database. Results. Of the 35 380 members who had weight data available at 12 months after joining, 69.1% (n=24 447)had a starting BMI≥30kg/m2. Their mean weight loss was 12.9±7.8% and for both sexes, weight loss at 12 months was greater for those who set targets (p25% was 7.6±4.0 kg/m2. A higher percentage of obese members did not set targets (p<0.001) compared to those with a BMI below 30kg/m2. Conclusions. Much of the variance in achieved weight loss in this population was explained by the number of targets set and the size of the first target. Whilst obese people were less likely to set targets, doing so increased the likelihood of achieving clinically significant weight loss and for some ‘unrealistic’ targets improved results

Comparison of food and nutrient intake in infants aged 6–12 months, following baby-led or traditional weaning: A cross-sectional study

Background: A baby-led approach to weaning (BLW) encompasses self-feeding and self-selecting graspable foods, offering an alternative to traditional weaning (TW). This cross-sectional study explored adherence to characteristics of BLW and differences in food group exposure and nutrient intake between babies following either TW or BLW. Methods: Nutritional data were collected via multiple-pass 24-h recall, following parental completion of an online survey. Results: Infants were grouped according to age (6–8 months; TW [n = 36] and BLW [n = 24]) and (9–12 months; TW [n = 24] and BLW [n = 12]). BLW babies were more likely to be breast fed (p = 0.002), consumed a higher percentage of foods also consumed by their mother (p = 0.008) and were fed less purees (p < 0.001) at 6–8 months. TW babies were spoon fed more (p ≤ 0.001) at all ages. Amongst babies aged 6–8 months, total intake (from complementary food plus milk) of iron (p = 0.021), zinc (p = 0.048), iodine (p = 0.031), vitamin B12 (p = 0.002) and vitamin D (p = 0.042) and both vitamin B12 (p = 0.027) and vitamin D (p = 0.035) from complementary food alone was higher in babies following TW. Compared to TW, BLW babies aged 6–8 months had a higher percentage energy intake from fat (p = 0.043) and saturated fat (p = 0.026) from their milk. No differences in nutrient intake were observed amongst infants aged 9–12 months. Few differences were observed between groups in their number of exposures to specific food groups. Conclusions: TW infants had higher intakes of key micronutrients at 6–8 months, although there were few differences in nutritional intake at 9–12 months or food group exposure between babies following TW or BLW. BLW appears to be socially desirable. Guidance for parents is required, along with larger, longer-term studies, which explore the potential impact of BLW in later childhood

The Effects of Prenatal Protein Restriction on β-Adrenergic Signalling of the Adult Rat Heart during Ischaemia Reperfusion

A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR) and related this to cardiac expression of β-adrenergic receptors (β-AR) and their associated G proteins. Pregnant rats were fed control (CON) or MLP diets (n = 12 each group) throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP) and dP/dtmax (P < 0.01) during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β2-AR following reperfusion and urinary excretion of noradrenaline and dopamine was lower in MLP and CON female rats versus CON males. In conclusion, the improved cardiac recovery in MLP male offspring following IR was attributed to greater membrane expression of β2-AR and reduced noradrenaline and dopamine levels. In contrast, females exhibiting both decreased membrane expression of β2-AR and catecholamine levels were protected from IR injury

Magnesium deficiency heightens lipopolysaccharide-induced inflammation and enhances monocyte adhesion in human umbilical vein endothelial cells

Given a possible anti-inflammatory role of magnesium in endothelial cells, the aim of this study was to investigate the effects of magnesium on human umbilical vein endothelial cell (HUVEC) viability, gene expression, and the pro-inflammatory response caused by a bacterial endotoxin (LPS). HUVECs were cultured at three different concentrations of magnesium sulphate (0.1mM; control-1mM; 5mM) for 72 hours. Exposing the cells to LPS reduced cell viability in culture with low magnesium, but high magnesium protected the HUVECs from LPS-induced cell death. LPS-treated HUVECs cultured in low magnesium showed up-regulation of mRNA expression for pro-inflammatory factors and the expression of cytokine proteins, including IL-2, IL-3, IL-8, IL-15 and MCP-1. This was associated with greater adhesion of monocytes to the cells. In contrast, high magnesium decreased the expression of inflammatory factors and cytokines. The study found that LPS activation of the expression of many pro-inflammatory factors is exacerbated in the presence of low magnesium concentration whilst a high magnesium concentration partly inhibited the inflammatory response to LPS

The impact of cafeteria feeding during lactation in the rat on novel object discrimination in the offspring

There is increasing evidence that hyperenergetic diets impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a cafeteria diet 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 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 1h, but not 2 or 4h. CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2h ITI. In contrast, control females exhibited discrimination following both 1 and 2h ITIs, but CD impaired performance. In summary, the present study shows that maternal exposure to 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