My review in the Journal of Human Nutrition and Dietetics entitled, Nutrition in early life and the programming of adult disease: a review has been receiving a lot of attention apparently. Not only was it the most downloaded paper in the journal in 2015 and second most downloaded in 2016, it is listed by InCites Essential Science Indicators as a Highly Cited Paper. That’s good news on a slow day.
As of July/August 2016, this highly cited paper received enough citations to place it in the top 1% of the academic field of Clinical Medicine based on a highly cited threshold for the field and publication year.
MAGIC is our longitudinal study of antenatal weight and postpartum weight retention which recruited in Nottingham. A number of outputs are due to come out of the study, but the first has now been accepted for publication in the Journal of Pregnancy.
The paper is entitled ‘Antenatal weight management: women’s experiences, behaviours, and expectations of weighing in early pregnancy’ and the authors were, Judy Swift, Jo Pearce, Preeti Jethwa, Moira Taylor, Amanda Avery, Sarah Ellis, Simon Langley-Evans and Sarah McMullen. The work was part-funded by a donation from the Revere Charitable Trust.
The current emphasis on obstetric risk management helps to frame gestational weight gain as problematic and encourages intervention by healthcare professionals. However pregnant women have reported confusion, distrust, and negative affect associated with antenatal weight management interactions. The MAGIC study (MAnaging weiGht In pregnanCy) sought to examine women’s self-reported experiences of usual-care antenatal weight management in early pregnancy, and consider these alongside weight monitoring behaviours and future expectations. 193 women (18yrs+) were recruited from routine antenatal clinics at the Nottingham University Hospital NHS Trust. Self-reported gestation was 10-27 weeks, with 41.5% (n=80) between 12-14 and 43.0% (n=83) between 20-22 weeks. At recruitment 50.3% of participants (n=97) could be classified as overweight or obese. 69.4% of highest weight women (≥30kg/m2) did not report receiving advice about weight, although they were significantly more likely to compared to women with BMI<30kg/m2. The majority of women (regardless of BMI) did not express any barriers to being weighed and 40.8% reported weighing themselves at home. Women across the BMI categories expressed a desire for more engagement from healthcare professionals on the issue of bodyweight. Women are clearly not being served appropriately in the current situation which simultaneously problematizes and fails to offer constructive dialogue.
Our paper entitled ‘Impact of gonadectomy on blood pressure regulation in ageing male and female rats’, has been accepted by Biology of Sex Differences (IF 3.23). The full author list is Wioletta Pijacka, Bethan Clifford, Dawid Walas, Chantal Tilburgs, Jaap A. Joles, Sarah McMullen and Simon C. Langley-Evans
This work was funded by the British Heart Foundation through a grant to Sarah McMullen and myself and is the product of a collaboration with Jaap in the Netherlands. The data give strong support to the hypothesis that testosterone has a major negative impact upon the health of males as they age.
Sexual dimorphism in blood pressure has been associated with differential expression of the angiotensin II (AII) receptors and with activity of the nervous system. It is generally accepted that aging affects kidney function as well as autonomic nervous system and hormonal balance. Given that hypertension is more prevalent in men than women until women reach their seventh decade we hypothesised that females would be relatively protected from adverse effects of ageing compared to males, and that this would be mediated by the protective effect of ovarian steroids. Intact and gonadectomised male and female normotensive Wistar rats aged 6, 12 and 18 months were used to study renal function, blood pressure, heart rate and blood pressure variability. We observed that intact females had lower levels of proteinuria and higher (12.5%) creatinine clearance compared to intact males, and that this difference was abolished by castration but not by ovariectomy. Ovariectomy resulted in a change by 9% in heart rate, resulting in similar cardiovascular parameters to those observed in males or gonadectomised males. Spectral analysis of systolic blood pressure revealed that high frequency power spectra were significantly elevated in the females vs. males and were reduced by ovariectomy. Taken altogether the results show that females are protected from age-related declining renal function and to a lesser extent from rising blood pressure in comparison to males. Whilst ovariectomy had some deleterious effects in females, the strongest effects were associated with gonadectomy in males, suggesting a damaging effect of male hormones.
In a few weeks time we will be joined by new PhD student Fiona Sach, who is funded through a NERC Envision Doctoral Training Programme, the Hermes Trust and Royal Society International Exchange scheme. Her project is supervised through Lisa Yon in the Vet School at Nottingham, Martin Broadley and myself in the School of Biosciences and is linked to the British Geological Survey with Michael Watts and Melanie Leng. Fiona will be focusing on mineral nutrition in captive and wild elephants.
Fiona has posted her own blog about the project here.
Our paper on the effect of maternal protein restriction on the rodent placental transcriptome has been accepted for publication in Genes and Nutrition. This work stems from studies originally performed by Angie Swali six years ago, with more recent RNA Sequencing analysis identifying differential regulation of genes involved in placental cholesterol transport as one of the possible mediators of developmental programming. The most recent elements of this project were funded by the Rosetrees Trust.
The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport.
Zoe Daniel, Angelina Swali, Richard Emes, Simon Langley-Evans
Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA Sequencing performed using the Illumina platform. Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life.
Our paper on setting weight loss targets in a commercial weight management group has been accepted for publication in the Journal of Human Nutrition and Dietetics. It will be available through the journal website within 6 weeks- see Early View.
Setting targets leads to greater long-term weight losses and ‘unrealistic’ targets increase the effect in a large community-based commercial weight management group.
Amanda Avery, Michaela Carrington, Simon Langley-Evans and Judy Swift
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 (p<0.001). Those that set ≥ 4 targets achieved the greatest loss (p<0.001). OR for weight loss ≥10% at 12 months was 10.3 (CI 9.7- 11.1, p<0.001) where targets had been set compared to none. At the highest quintile of target size, the size of the first target explained 47.2% (p<0.001) of the variance in weight loss achieved at 12 months. The mean BMI reduction in those with a target >25% 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.
Our paper entitled Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse has been accepted for publication by the Journal of the Developmental Origins of Health and Disease. Study authors are Liz Tarling, Ruth Austin, Kevin Ryan, Susanne Kugler, Simon Langley-Evans and Andy Salter.
The paper describes the impact of feeding a high fat diet during pregnancy upon development of atherosclerosis in the adult ApoE*3 Leiden offspring of wild type mice. ApoE*3 Leiden mice are mice carrying a human mutation of the ApoE gene. This gene predisposes to atherosclerosis in mice that are fed a high cholesterol diet. In our study transgenic males were mated with wild type females and the pregnant mice were either fed a low fat or a high fat ‘Western’ type diet. Atherosclerosis prone ApoE*3 Leiden female offspring were then fed either low fat, low cholesterol diet or a high cholesterol atherogenic diet.
All mice fed the atherogenic diet developed atherosclerotic plaques, but those whose mothers were fed the high fat diet developed significantly larger plaques. This study confirms our earlier work that showed that maternal diet during pregnancy can programme atherosclerosis in the offspring, but importantly showed that a typical high fat Western diet is as effective in this programming as is undernutrition (our previous work showed programming by feeding a low protein diet). The data are consistent with the hypothesis that maternal fat intake may result in the development of atherosclerotic plaques during fetal development, but other mechanisms may be at work, including programming of inflammatory processes.