Andrew M. Prentice

Obesity in Britain: gluttony or sloth?

The prevalence of clinical obesity in Britain has doubled in the past decade. The Health of the Nation initiative has set ambitious targets for reversing the trend in recognition of the serious health burden which will accrue, but efforts to develop prevention and treatment strategies are handicapped by uncertainty as to the aetiology of the problem. It is generally assumed that ready access to highly palatable foods induces excess consumption and that obesity is caused by simple gluttony. There is evidence that a high fat diet does override normal satiety mechanisms. However, average recorded energy intake in Britain has declined substantially as obesity rates have escalated. The implication is that levels of physical activity, and hence energy needs, have declined even faster. Evidence suggests that modern inactive lifestyles are at least as important as diet in the aetiology of obesity and possibly represent the dominant factor.

High levels of energy expenditure in obese women

Total free living energy expenditure was compared in lean and obese women by the new doubly labelled water method and partitioned into basal metabolism and thermogenesis plus activity by whole body calorimetry. Average energy expenditure was significantly higher in the obese group (10.22 versus 7.99 MJ/day (2445 versus 1911 kcal/day); p less than 0.001) resulting from an increase in the energy cost of both basal metabolism and physical activity. Self recorded energy intakes were accurate in the lean subjects but underestimated expenditure by 3.5 MJ/day (837 kcal/day) in the obese group. Basal metabolic rate and energy expenditure on thermogenesis plus activity were identical in the two groups when corrected for differences in fat free mass and total body mass. In the obese women in this series there was no evidence that their obesity was caused by a metabolic or behavioural defect resulting in reduced energy expenditure.

Body fat reference curves for children

Objective:To refine the diagnosis of childhood obesity by creating new sex-specific centile curves for body fat and to base these references on a simple and affordable method that could be widely adopted in clinical practice and surveys.Design:Body fat was measured by bio-impedance in 1985 Caucasian children aged 5–18 years from schools in Southern England. Smoothed centile charts were derived using the LMS method.Results:The new body fat curves reflect the known differences in the development of adiposity between boys and girls. The curves are similar by sex until puberty but then diverge markedly, with males proportionately decreasing body fat and females continuing to gain. These sex differences are not revealed by existing curves based on body mass index. We present charts in which cutoffs to define regions of ‘underfat’, ‘normal’, ‘overfat’ and ‘obese’ are set at the 2nd, 85th and 95th centiles. These have been designed to yield similar proportions of overweight/overfat and obese children to the IOTF body mass index cutoffs.Conclusions:Direct assessment of adiposity, the component of overweight that leads to pathology, represents a significant advance over body mass index. Our new charts will be published by the Child Growth Foundation for clinical monitoring of body fat, along with the software to convert individual measurements to Z-scores.

Measurements of total energy expenditure provide insights into the validity of dietary measurements of energy intake

The quantification of errors inherent in methods of measuring dietary intake has been handicapped by the absence of independent markers for testing their validity. The doubly labeled water technique permits a precise measure of energy expenditure in free-living persons. Because energy expenditure must equal energy intake in populations in energy balance, this technique may be used to validate the assessment of energy intake. A series of studies demonstrated good agreement between mean energy intake and mean energy expenditure when food intake was recorded by observers or when it was self-reported by normal-weight, self-selected, highly motivated volunteer subjects using weighed records. However, in randomly recruited men and women, energy intake by weighed records was 82% and 81%, of energy expenditure, respectively, indicating underestimation of habitual intake. Men and women in the lowest third of reported intake recorded energy expenditure of only 69% and 61%, respectively. Reported intake of obese and previously obese women was only 73% and 64% of expenditure, whether measured by weighed record or by diet history, confirming suspicions that these subjects misrepresented their intake. Acceptable weighed records were obtained from 7- and 9-year-olds whereas 15- and 18-year-olds underestimated intake. Diet histories taken from the same children tended to overestimate intake. These studies suggest that, ideally, all dietary studies should include independent measures of validity.

Energy Expenditure and Wasting in Human Immunodeficiency Virus Infection

BACKGROUND Increased expenditure of energy at rest has been considered a contributing factor to the negative energy balance and weight loss that occur in patients with human immunodeficiency virus (HIV) infection. However, the true determinant of energy balance is not resting but total energy expenditure. We sought to determine the contribution of total energy expenditure to weight changes in patients with HIV-associated wasting. METHODS We performed 51 assessments of energy metabolism in 27 men with HIV infection at different stages of disease, including periods of both rapid and slow weight loss. Resting energy expenditure was measured by indirect calorimetry, total energy expenditure by the doubly-labeled-water technique, and energy intake by recording the weight of food consumed. The results were compared with the rate of weight loss or gain. RESULTS The mean (+/- SD) total energy expended by the HIV-infected men was 2750 +/- 670 kcal per day, no more than that expended by normal men. There was a significant positive relation between total energy expenditure and the rate of weight change (r = 0.61, P < 0.001); thus, during rapid weight loss, total energy expenditure was reduced to 2180 +/- 580 kcal per day (P = 0.009), primarily because of reduced physical activity. During rapid weight loss, the negative energy balance (-850 +/- 580 kcal per day) was primarily the result of the reduction in energy intake, to 1330 +/- 610 kcal per day; intake correlated strongly with the rate of weight change (r = 0.84, P < 0.001). CONCLUSIONS In patients with HIV infection, total energy expenditure is reduced during episodes of weight loss. Reduced energy intake, not elevated energy expenditure, is the prime determinant of weight loss in HIV-associated wasting.

Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial .

Abstract Objective: To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system. Design: 5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control). Setting: Rural Gambia. Subjects: Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths. Main outcome measures: Birth weight; prevalence of low birth weight (<2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality. Results: Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P<0.001) in the hungry season, by 94 g (P<0.01) in the harvest season (November to May), and by 136 g (P<0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P<0.001). Head circumference was significantly increased (P<0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P<0.05) for stillbirths and 0.54 (0.35 to 0.85, P<0.01) for all deaths in first week of life. Mortality after 7 days was unaffected. Conclusion: Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system. Key messages In developing countries chronic maternal undernutrition is a prime contributor to the birth of over 25 million low birthweight babies annually and to high rates of neonatal mortality. An absence of well designed field trials has created uncertainty about the potential efficacy of maternal feeding programmes This large scale randomised controlled trial shows that dietary supplementation in pregnancy can be highly effective in reducing the proportion of low birthweight babies and perinatal mortality Incorporating supplementary feeding into a rural primary healthcare system is feasible Late pregnancy is the period most amenable to intervention

Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles

Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease.

Hepcidin and the Iron-Infection Axis

Double-Edged Iron Hepcidin is a small peptide hormone discovered by three groups investigating iron-regulated liver genes and antimicrobial peptides. This new hormone turned out not only to regulate iron but also to have homology with peptides required for innate immune responses. Drakesmith and Prentice (p. 768) review the importance of hepcidin during infection, explaining how it is involved in withholding iron from microbial pathogens to curtail replication and how intracellular bacteria are able to thwart this host response. Recent work highlights the potential hazards of iron-supplementation in infection, particularly in malaria, whereby an overload of iron, meant to treat malaria-induced anemia, may negate the protective effects of hepcidin. Iron lies at the center of a battle for nutritional resource between higher organisms and their microbial pathogens. The iron status of the human host affects the pathogenicity of numerous infections including malaria, HIV-1, and tuberculosis. Hepcidin, an antimicrobial-like peptide hormone, has emerged as the master regulator of iron metabolism. Hepcidin controls the absorption of dietary iron and the distribution of iron among cell types in the body, and its synthesis is regulated by both iron and innate immunity. We describe how hepcidin integrates signals from diverse physiological inputs, forming a key molecular bridge between iron trafficking and response to infection.

Energy and transport

We examine the links between fossil-fuel-based transportation, greenhouse-gas emissions, and health. Transport-related carbon emissions are rising and there is increasing consensus that the growth in motorised land vehicles and aviation is incompatible with averting serious climate change. The energy intensity of land transport correlates with its adverse health effects. Adverse health effects occur through climate change, road-traffic injuries, physical inactivity, urban air pollution, energy-related conflict, and environmental degradation. For the worlds poor people, walking is the main mode of transport, but such populations often experience the most from the harms of energy-intensive transport. New energy sources and improvements in vehicle design and in information technology are necessary but not sufficient to reduce transport-related carbon emissions without accompanying behavioural change. By contrast, active transport has the potential to improve health and equity, and reduce emissions. Cities require safe and pleasant environments for active transport with destinations in easy reach and, for longer journeys, public transport that is powered by renewable energy, thus providing high levels of accessibility without car use. Much investment in major road projects does not meet the transport needs of poor people, especially women whose trips are primarily local and off road. Sustainable development is better promoted through improving walking and cycling infrastructures, increasing access to cycles, and investment in transport services for essential needs. Our model of London shows how increased active transport could help achieve substantial reductions in emissions by 2030 while improving population health. There exists the potential for a global contraction and convergence in use of fossil-fuel energy for transport to benefit health and achieve sustainability.

Towards a new developmental synthesis: adaptive developmental plasticity and human disease

1focusing mainly on short-term outcomes such as infant survival and stunting. 2 However, the longer term eff ects on adult health 3 of a poor start to life suggest a further perspective. Developmental eff ects have been viewed traditionally in the context of major disruptions such as caused by teratogens, prematurity and growth retardation, but there is increasing appreciation of the role of developmental plasticity, which provides individuals with the fl exibility to adjust their trajectory of development to match their environment. Plasticity operates across the entire range of environment, from undernutrition to excessive nutritional environments associated with gestational diabetes or maternal obesity, 4,5