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Non-alcoholic fatty liver disease encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. The liver plays a major role in regulating fatty acid metabolism and perturbations in intrahepatic processes have potential to impact on metabolic health. It remains unclear why intra-hepatocellular fat starts to accumulate, but it likely involves an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and TAG export from the liver. As man spends the majority of the day in a postprandial rather than postabsorptive state, dietary fatty acid intake should be taken into consideration when investigating why intra-hepatic fat starts to accumulate. This review will discuss the impact of the quantity and quality of dietary fatty acids on liver fat accumulation and metabolism, along with some of the potential mechanisms involved. Studies investigating the role of dietary fat in liver fat accumulation, although surprisingly limited, have clearly demonstrated that it is total energy intake, rather than fat intake per se, that is a key mediator of liver fat content; hyperenergetic diets increase liver fat whilst hypoenergetic diets decrease liver fat content irrespective of total fat content. Moreover, there is now, albeit limited evidence emerging to suggest the composition of dietary fat may also play a role in liver fat accumulation, with diets enriched in saturated fat appearing to increase liver fat content to a greater extent when compared with diets enriched in unsaturated fats.
Currently the world is facing an incredibly costly epidemic of obesity. Almost two-thirds of UK adults are either overweight or obese with estimated financial costs to the UK economy alone of £27 billion per year. While fundamentally obesity is a disorder of energy balance, several decades of research has demonstrated that maintaining energy balance is much more complex than the ‘energy in equals energy out’ equation that was once touted. The purpose of the 2018 Nutrition Society Summer Conference, ‘Getting energy balance right’ was to provide insight into the numerous factors influencing energy balance, considering varying needs across the lifespan, while highlighting advances and gaps in knowledge. Papers presented in this issue illustrate the wide range of factors involved in maintaining energy balance, including: epigenetics, the gut microbiome, physical activity and dietary factors including sugar. Given the complexity of energy balance, systems approaches were highlighted as useful for both understanding metabolism and pathophysiology, and for understanding how public health interventions to treat and prevent obesity should be implemented. The meeting concluded that numerous stakeholders, from individuals, to schools, industry and government, have roles to play in fostering a positive food environment that facilitates the maintenance of energy balance throughout the lifespan.
Consumption of sugar and alternative low- or no-energy sweeteners has increased in recent decades. However, it is still uncertain how consumption of sugar and alternative sweeteners during pregnancy affects pregnancy outcomes and long-term offspring health. This review aims to collate the available evidence surrounding the consequences of sugar and alternative sweetener consumption during pregnancy, a so-called secondhand sugar effect. We found evidence that sugar consumption during pregnancy may contribute to increased gestational weight gain and the development of pregnancy complications, including gestational diabetes, preeclampsia and preterm birth. Further, we found a growing body of the animal and human evidence that maternal sugar intake during pregnancy may impact neonatal and childhood metabolism, taste perception and obesity risk. Emerging evidence also suggests that both maternal and paternal preconception sugar intakes are linked to offspring metabolic outcomes, perhaps via epigenetic alterations to the germline. While there have been fewer studies of the impacts of alternative sweetener consumption before and during pregnancy, there is some evidence to suggest effects on infant outcomes including preterm birth risk, increased infant body composition and offspring preference for sweet foods, although mechanisms are unclear. We conclude that preconception and gestational sugar and alternative sweetener consumption may negatively impact pregnancy outcomes and offspring health and that there is a need for further observational, mechanistic and intervention research in this area.
Symposium 1: Regulation of energy balance and whole body metabolism
Animal models are valuable for the study of complex behaviours and physiology such as the control of appetite because genetic, pharmacological and surgical approaches allow the investigation of underlying mechanisms. However, the majority of such studies are carried out in just two species, laboratory mice and rats. These conventional laboratory species have been intensely selected for high growth rate and fecundity, and have a high metabolic rate and short lifespan. These aspects limit their translational relevance for human appetite control. This review will consider the value of studies carried out in a seasonal species, the Siberian hamster, which shows natural photoperiod-regulated annual cycles in appetite, growth and fattening. Such studies reveal that this long-term control is not simply an adjustment of the known hypothalamic neuronal systems that control hunger and satiety in the short term. Long-term cyclicity is probably driven by hypothalamic tanycytes, glial cells that line the ventricular walls of the hypothalamus. These unique cells sense nutrients and metabolic hormones, integrate seasonal signals and effect plasticity of surrounding neural circuits through their function as a stem cell niche in the adult. Studies of glial cell function in the hypothalamus offer new potential for identifying central targets for appetite and body weight control amenable to dietary or pharmacological manipulation.
This review examines the metabolic adaptations that occur in response to negative energy balance and their potential putative or functional impact on appetite and food intake. Sustained negative energy balance will result in weight loss, with body composition changes similar for different dietary interventions if total energy and protein intake are equated. During periods of underfeeding, compensatory metabolic and behavioural responses occur that attenuate the prescribed energy deficit. While losses of metabolically active tissue during energy deficit result in reduced energy expenditure, an additional down-regulation in expenditure has been noted that cannot be explained by changes in body tissue (e.g. adaptive thermogenesis). Sustained negative energy balance is also associated with an increase in orexigenic drive and changes in appetite-related peptides during weight loss that may act as cues for increased hunger and food intake. It has also been suggested that losses of fat-free mass (FFM) could also act as an orexigenic signal during weight loss, but more data are needed to support these findings and the signalling pathways linking FFM and energy intake remain unclear. Taken together, these metabolic and behavioural responses to weight loss point to a highly complex and dynamic energy balance system in which perturbations to individual components can cause co-ordinated and inter-related compensatory responses elsewhere. The strength of these compensatory responses is individually subtle, and early identification of this variability may help identify individuals that respond well or poorly to an intervention.
Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25–30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.
Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression. Epigenetic processes regulate the accessibility of genes to the cellular proteins that control gene transcription, determining where and when a gene is switched on and its level of activity. Epigenetic processes not only play a central role in regulating gene expression but also allow an organism to adapt to the environment. In this review, we will focus on how both maternal and paternal nutrition can alter the epigenome and the evidence that these changes are causally involved in determining future disease risk.
Symposium 2: Molecular mechanisms contributing to energy balance
Dietary intake and nutritional status is an important environmental factor which can modulate metabolic-inflammation. In recent years, research has made significant advances in terms of understanding the impact of dietary components on metabolic-inflammation, within the context of obesity, type-2 diabetes (T2D) and CVD risk. Our work demonstrated that different fatty acids differentially modulate metabolic-inflammation, initially focusing on Nod-like receptor family, pyrin domain-containing three protein (NLRP3) inflammasome mediated IL-1β biology and insulin signalling. However, the paradigm is more complex, wherein data from the immunology field clearly show that nature of cellular energy metabolism is a key determinant of inflammation. Whilst metabolic-inflammation is a critical biological interaction, there is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation. The complex paradigm will be discussed within the context of if/how dietary components, in particular fatty acids, may modulate obesity, T2D and CVD risk, via inflammatory and metabolic processes.
This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut–liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.
Ageing population suffer from increased risk of malnutrition which is a major determinant of accelerated loss of autonomy, adverse health outcomes and substantial health-care costs. Malnutrition is largely attributed to reduced nutrient intake which may be associated with several endogenous factors, such as decline of muscle mass, oral functions and coordination that can make the eating process difficult. From an exogenous viewpoint, nutritionally dense foods with limited innovations in food texture have been traditionally offered to elderly population that negatively affected pleasure of eating and ultimately, nutrient intake. Recent research has recognised that older adults within the same age group are not homogenous in terms of their preferences, nutritional needs, capabilities and impediments in skill-sets. Hence, a new term eating capability (EC) has been coined to describe various quantifiable endogenous factors in the well-coordinated eating process that may permit characterisation of the capabilities of elderly individuals in food handling and oral processing. This review covers current knowledge on EC focusing on parameters, such as hand and oro-facial muscle forces. Although limited in literature, EC score measured using a comprehensive toolkit has shown promise to predict eating difficulty perception and oral processing behaviour. Further systematic studies are required to explore relationships between individual/multiple constituents of EC and oral comfort. Such knowledge base is needed to underpin the creation of next generation personalised texture-modified foods for elderly population using sophisticated technologies, such as 3D printing to enhance eating pleasure, increase nutrient intake that will ultimately contribute to tackling malnutrition.
Some food bioactives potentially exert anti-obesity effects. Anthocyanins (ACN), catechins, β-glucan (BG) and n-3 long chain PUFA (LCPUFA) are among the most promising candidates and have been considered as a strategy for the development of functional foods counteracting body weight gain. At present, clinical trials, reviews and meta-analyses addressing anti-obesity effects of various bioactives or bioactive-rich foods show contradictory results. Abdominal obesity is an important criterion for metabolic syndrome (MetS) diagnosis along with glucose intolerance, dyslipidaemia and hypertension. Food bioactives are supposed to exert beneficial effects on these parameters, therefore representing alternative therapy approaches for the treatment of MetS. This review summarises outcomes on MetS biomarkers in recent clinical trials supplementing ACN, catechins, BG and n-3 LCPUFA, focusing mainly on anti-obesity effects. Overall, it is clear that the level of evidence for the effectiveness varies not only among the different bioactives but also among the different putative health benefits suggested for the same bioactive. Limited evidence may be due to the low number of controlled intervention trials or to inconsistencies in trial design, i.e. duration, dose and/or the method of bioactive supplementation (extracts, supplements, rich or enriched food). At present, the question ‘Are bioactives effective in weight management and prevention of metabolic syndrome?’ remains inconclusive. Thus, a common effort to harmonise the study design of intervention trials focusing on the most promising bioactive molecules is urgently needed to strengthen the evidence of their potential in the treatment of obesity, MetS and related diseases.
Symposium 4: Nutritional epidemiology and risk of chronic disease
A mother's nutritional choices while pregnant may have a great influence on her baby's development in the womb and during infancy. There is evidence that what a mother eats during pregnancy interacts with her genes to affect her child's susceptibility to poor health outcomes including childhood obesity, pre-diabetes, allergy and asthma. Furthermore, after what an infant eats can change his or her intestinal bacteria, which can further influence the development of these poor outcomes. In the present paper, we review the importance of birth cohorts, the formation and early findings from a multi-ethnic birth cohort alliance in Canada and summarise our future research directions for this birth cohort alliance. We summarise a method for harmonising collection and analysis of self-reported dietary data across multiple cohorts and provide examples of how this birth cohort alliance has contributed to our understanding of gestational diabetes risk; ethnic and diet-influences differences in the healthy infant microbiome; and the interplay between diet, ethnicity and birth weight. Ongoing work in this birth cohort alliance will focus on the use of metabolomic profiling to measure dietary intake, discovery of unique diet–gene and diet–epigenome interactions, and qualitative interviews with families of children at risk of metabolic syndrome. Our findings to-date and future areas of research will advance the evidence base that informs dietary guidelines in pregnancy, infancy and childhood, and will be relevant to diverse and high-risk populations of Canada and other high-income countries.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease, affecting 10% of school-aged children and 44–70% of obese children and young people (CYP) in the western world. Encompassing a spectrum from simple steatosis to steatohepatitis and progressive fibrosis, the disease is rapidly becoming the most common indication for liver transplantation. The molecular pathogenesis of NAFLD remains only partially understood. Development and progression of NAFLD is influenced by genetic and nutritional factors, insulin resistance, oxidative stress, gut microbiome, bile acid metabolism and lipid/glucose handling and is closely associated with overweight and obesity. Lifestyle change is the only proven effective treatment for paediatric NAFLD, however this is difficult to achieve in many. Given that moderate or severe fibrosis is already present in 30–50% of children with NAFLD at the time of presentation, progression in CYP may be more rapid, though adequate outcome data do not yet exist in this cohort. CYP with NAFLD are an excellent population in which to study underlying mechanisms and interventions to correct disease progression as they are largely unaffected by other environmental influences such as alcohol and may represent the more severe end of the spectrum in terms of early onset. Undoubtedly genetic and epigenetic mechanisms determine a large proportion of susceptibility to the disease and potentially, identification of individuals at risk may allow for targeted therapy. This review with give a clinical perspective of paediatric NAFLD focused on identifying those at risk of progressive disease and what to consider in attempting to modify risk.
Older adults are at risk of protein-energy malnutrition (PEM). PEM detrimentally impacts on health, cognitive and physical functioning and quality of life. Given these negative health outcomes in the context of an ageing global population, the Healthy Diet for a Healthy Life Joint Programming Initiative Malnutrition in the Elderly (MaNuEL) sought to create a knowledge hub on malnutrition in older adults. This review summarises the findings related to the screening and determinants of malnutrition. Based on a scoring system that incorporated validity, parameters used and practicability, recommendations on setting-specific screening tools for use with older adults were made. These are: DETERMINE your health checklist for the community, Nutritional Form for the Elderly for rehabilitation, Short Nutritional Assessment Questionnaire-Residential Care for residential care and Malnutrition Screening Tool or Mini Nutritional Assessment-Short Form for hospitals. A meta-analysis was conducted on six longitudinal studies from MaNuEL partner countries to identify the determinants of malnutrition. Increasing age, unmarried/separated/divorced status (vs. married but not widowed), difficulties walking 100 m or climbing stairs and hospitalisation in the year prior to baseline or during follow-up predicted malnutrition. The sex-specific predictors of malnutrition were explored within The Irish Longitudinal Study of Ageing dataset. For females, cognitive impairment or receiving social support predicted malnutrition. The predictors for males were falling in the previous 2 years, hospitalisation in the past year and self-reported difficulties in climbing stairs. Incorporation of these findings into public health policy and clinical practice would support the early identification and management of malnutrition.
Symposium 5: Sustainability of food production and dietary recommendations
Climate change is threatening future global food and nutrition security. Limiting the increase in global temperature to 1·5 °C set out in The Paris Agreement (2015) while achieving nutrient security means overhauling the current food system to create one that can deliver healthy and sustainable diets. To attain this, it is critical to understand the implications for nutrition of actions to mitigate climate change as well as the impacts of climate change on food production and the nutrient composition of foods. It is widely recognised that livestock production has a much greater environmental burden than crop production, and therefore advice is to reduce meat consumption. This has triggered concern in some sectors about a lack of protein in diets, which hence is driving efforts to find protein replacements. However, in most high- and middle-income countries, protein intakes far exceed dietary requirements and it would even if all meat were removed from diets. Reduction in micronutrients should be given more attention when reducing meat. Simply eating less meat does not guarantee healthier or more sustainable diets. Climate change will also affect the type, amount and nutrient quality of food that can be produced. Studies have shown that increased temperature and elevated CO2 levels can reduce the nutrient density of some staple crops, which is of particular concern in low-income countries. Nutrition from a climate change perspective means considering the potential consequences of any climate action on food and nutrition security. In this paper, we discuss these issues from an interdisciplinary perspective.
Multiple forms of malnutrition co-exist (the double burden) in low- and middle-income countries, but most interventions and policies target only one form. Identifying shared drivers of the double burden of malnutrition is a first step towards establishing effective interventions that simultaneously address the double burden of malnutrition (known as double-duty actions). We identified shared drivers for the double burden of malnutrition, to assess which double-duty actions are likely to have the greatest reach in preventing all forms of malnutrition, in the context of the sustainable development goals. We reviewed existing conceptual frameworks of the drivers of undernutrition, obesity and environmental sustainability. Shared drivers affecting all forms of malnutrition and environmental sustainability were captured using a socio-ecological approach. The extent to which drivers were addressed by the five double-duty actions proposed by the WHO was assessed. Overall, eighty-three shared drivers for the double burden of malnutrition were identified. A substantial proportion (75·0%) could be addressed by the five WHO double-duty actions. ‘Regulations on marketing’ and ‘promotion of appropriate early and complementary feeding in infants’ addressed the highest proportion of shared drivers (65·1% and 53·0%, respectively). Twenty-four drivers were likely to be sensitive to environmental sustainability, with ‘regulations on marketing’ and ‘school food programmes and policies’ likely to have the greatest environmental reach. A quarter of the shared drivers remained unaddressed by the five WHO double-duty actions. Substantially more drivers could be addressed with minor modifications to the WHO double-duty actions and the addition of de novo actions.
The present paper results from my receiving the Nutrition Society's first Blaxter Award, and describes briefly my academic history. My interest in human fat metabolism began in the Medical Research Council's Trauma Unit, studying metabolic changes in critically ill patients and their responses to nutrition. On moving to Oxford in 1986, I began to study pathways for depositing fat in adipose tissue. This involved the development of new methodologies, in particular, a technique for measurement of arterio-venous differences of metabolite concentrations across human adipose tissue beds, primarily the subcutaneous anterior abdominal depot. Our early studies showed that this tissue is dynamic in its metabolic behaviour, responding rapidly (within minutes) to changes in nutritional state. This led to an understanding of adipose tissue as playing an essential role in metabolic health, by capturing incoming dietary fatty acids, storing them as TAG and releasing them when needed, analogous to the role of the liver in glucose metabolism; we called this ‘buffering’ of fatty acid fluxes. In obesity, the mass of adipose tissue expands considerably, more than is often appreciated from BMI values. We confirmed other observations of a strong suppression of release of NEFA from adipose tissue in obesity, tending to normalise circulating NEFA concentrations. A corollary, however, is that fatty acid uptake must be equally suppressed, and this disrupts the ‘buffering’ capacity of adipose tissue, leading to fat deposition in other tissues; ectopic fat deposition. This, in turn, is associated with many metabolic abnormalities linked to obesity.
The internet has considerable potential to improve health-related food choice at low-cost. Online solutions in this field can be deployed quickly and at very low cost, especially if they are not dependent on bespoke devices or offline processes such as the provision and analysis of biological samples. One key challenge is the automated delivery of personalised dietary advice in a replicable, scalable and inexpensive way, using valid nutrition assessment methods and effective recommendations. We have developed a web-based personalised nutrition system (eNutri) which assesses dietary intake using a validated graphical FFQ and provides personalised food-based dietary advice automatically. Its effectiveness was evaluated during an online randomised controlled trial dietary intervention (EatWellUK study) in which personalised dietary advice was compared with general population recommendations (control) delivered online. The present paper presents a review of literature relevant to this work, and describes the strategies used during the development of the eNutri app. Its design and source code have been made publicly available under a permissive open source license, so that other researchers and organisations can benefit from this work. In a context where personalised diet advice has great potential for health promotion and disease prevention at-scale and yet is not currently being offered in the most popular mobile apps, the strategies and approaches described in the present paper can help to inform and advance the design and development of technologies for personalised nutrition.
Coeliac disease (CD) is an autoimmune gastrointestinal disorder whereby the ingestion of gluten, a storage protein found in wheat, barley and rye, causes damage to intestinal mucosa with resultant malabsorption, increased risk of anaemia and osteoporosis. Worldwide estimates suggest 1% of the population have CD. With no cure, the only treatment is a gluten-free diet (GFD). Adhering to a GFD can be very challenging; it requires knowledge, motivation and modified behaviours. Assessing adherence to a GFD is methodologically challenging. This review aims to provide an overview of the literature reporting adherence to a GFD in people with CD and the methodological challenges encountered. From six studies it has been reported that rates of adherence to a GFD range between 45 and 90% in patients of different ethnicities with CD. GF dietary adherence can be influenced by age at diagnosis, coexisting depression, symptoms on ingestion of gluten, nutrition counselling, knowledge of GF foods, understanding of food labels, cost and availability of GF foods, receiving GF foods on prescription and membership of a coeliac society. To date only five intervention studies in adults with CD have been undertaken to improve GF dietary adherence. These have included dietary and psychological counselling, and the use of online training programmes, apps, text messages and telephonic clinics. Future interventions should include people of all ethnicities, consider patient convenience and the cost-effectiveness for the healthcare environment.
Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.