Emulsion structure: a novel mechanism of delivering fatty acids to regulate gut function and satiety.

Obesity and associated conditions, such as cardiovascular disease, type II diabetes and some cancers, are one of the greatest challenges facing the health of the UK population. This is due to a combination of dietary and lifestyle factors. If our physical activity is decreasing, then so should dietary energy intake. However, several factors make it difficult for us to restrict our food intake, including:- evolutionary pressure to consume excess food, the constant, year-round availability and choice of cheap, convenient and desirable, high energy foods. It is therefore unsurprising that many individuals find it difficult to restrict their food intake. As a consequence, there has been much recent interest in designing foods which reduce appetite or promote satiety as an aid to control dietary intake and prevent the onset of obesity. However, to date there have been no effective foods developed that can reduce body weight in humans. Designing foods which target physiological mechanisms controlling appetite may provide a novel way of treating obesity. This project is based on the principle that slowing fat digestion will stimulate hormone secretion from the gut that reduce appetite as follows:- - Normally, most nutrients are absorbed in the first section of the small intestine (the duodenum). - Large or difficult to digest meals allow some nutrients to travel to the end of the small intestine (the ileum) - These nutrients stimulate cells in the wall of the ileum to secrete appetite suppressing hormones. - These hormones slow down digestion and reduce hunger. We will test the hypothesis that inhibiting fat digestion in rationally designed emulsions to deliver specific types of fat to the lower small intestine, will reduce appetite. We do not wish to stop fat digestion completely, as this can lead to side effects such as fatty diarrhoea (steatorrhea). We have already shown that we can slow fat digestion in the laboratory by coating the surface of fat droplets with plant lipids (galactolipids) or enzyme treated milk proteins. These molecules make surface of the fat droplets in emulsions, resistant to the processes involved in fat digestion. We now want to apply these findings to human studies so we can determine how these molecules work and measure their effects on lipid digestion, hormone release, and food intake. Our main objectives are: 1. Determine which specific lipid molecules are the most effective at stimulating hormone secretion. 2. Design model emulsion systems which both delay fat digestion, and deliver certain types of lipid to the lower small intestine in model systems. 3. Quantify the outcomes on healthy human volunteers by measuring lipid digestion rates, gut hormone release and appetite levels. The emulsions will be designed and undergo in vitro digestions at the Institute of Food Research based on over 20 years research experience in food emulsions and interfaces. Measurements of gut hormone secretion will be undertaken at Imperial College London, whose researchers are one of the leading groups in the world on gut hormones. The digestion of fats in humans will be determined at the Scottish Universities Environmental Research Centre in Glasgow, a leading centre in its field. Experiments determining the effects satiety in humans will be performed in conjunction with the world renowned department of psychology at the University of Leeds. This project will determine the design principles involved in formulating a wide variety of foods, including everyday, desirable foods with true, verifiable, satiety promoting properties that will benefit all sectors of the population. The research would lead to further, longer term projects to verify that such foods have utility in long term weight control.

Obesity and associated health problems have in part been linked with chronic overconsumption, leading to gradual long term weight gain and obesity. Enhancing the satiety promoting properties of a wide range of common food products offers a sustainable solution. However, the complex mechanisms involved in the digestion of and subsequent physiological response to these structures is not known. This study aims to delay lipid digestion by designing the interfaces of fat droplets to modulate lipolysis. This will enable delivery of fatty acids to the distal small intestine to promote secretion of satiety inducing hormones in humans and hence reduce appetite. This will help develop a rational design strategy for satiety promoting foods as a long term weight control strategy. We have previously demonstrated delayed lipolysis in vitro by creating emulsion droplets stabilised by galactolipids or crosslinked proteins which increase resistance to lipolysis by preventing adsorption of bile salts and/or lipase/colipase. The next stage of this research is to determine the effectiveness in vivo. Therefore this study will aim to address the following objectives:- 1. Identify which specific lipids are most effective at stimulating anorectic gut hormones in cellular and animal models. 2. Determine how rational design of emulsions (form and composition) can resist lipid digestion and target the delayed release of specific lipids to the lower small intestine in vitro and in animal models. 3. Validate the effectiveness of the emulsion systems on healthy human volunteers by quantifying the impact on lipid digestion rates, gut hormone release and satiety. The outcome of this study will be to determine the mechanistic pathways, both physiological and physico-chemical, that control satiety through the rational design of resistant emulsion systems. The design principles involved will be used to develop human studies to determine the impact on long weight control.

This research addresses one of the main diet-related health challenges currently facing the developed world, and therefore has huge potential long term impact on a wide range of stakeholders from consumers to policy makers. In addition to the academic beneficiaries listed above, the outputs of the research will impact on the following stakeholder groups:- Food Industry: This sector will benefit from the knowledge to potentially aid the design of a new generation of satiety promoting foods with proven effects on appetite, and, if demonstrated through long term weight control studies, positive effects on weight control. Further research will allow the generic design principles to be incorporated into a wide range of food and beverages. Satiety promoting food is a growing sector of the food industry and robust scientific evidence of positive health benefits will support further growth and give the UK food industry a competitive advantage. The generic knowledge produced will allow approaches to be developed to improve delivery of lipid soluble nutrients from foods and functional foods. Consumers: Individuals will have a wider choice of foods with specific, proven health benefits. The foods ought to have comparable consumer acceptability, making it more convenient for consumers to adopt a healthier lifestyle. The long term benefits of reduced weight gain will lower the incidence of overweight and obese individuals and ought to reduce the incidence of associated conditions such as high blood pressure, cardiovascular disease, diabetes and some cancers. This will clearly be of benefit to the ageing population, improving the quality of life into old age. Pharmaceutical Industry: The generic principles involved will stimulate further research to enable strategies to be developed to improve the delivery of lipid soluble drugs. This will result in more effective therapies that will also benefit consumers. National Health Service: The direct costs to the NHS and other health care providers for treating obesity and related conditions is currently around £1billion per year. This is rising steeply due to the increased use of bariatric surgery to reduce dietary intake (over 4000 cases in 2008/09, more than double that in 2006/07). The long term benefits of a less obese population would be fewer admissions, fewer surgical interventions and fewer prescriptions, which would clearly have an impact on NHS costs. Government: The associated costs of obesity to the nation are considered to be higher than the direct costs of treatment. The subsequent loss of working days due to sickness as a result of obesity and related conditions is estimated at around 18 million sick days per year and loss of productivity is estimated to cost the nation more than £2billion pa. Implementation: The main routes for implementing these benefits are initially through dissemination and further research. Dissemination activities will be in the form of publications in high impact journals and international conferences to increase the opportunities for further funding. Dissemination to industry is very important, so publications will be made through partners newsletters and websites. IFRs Food & Health Network will be used to directly communicate the research to industry. The further research will be sought to study the longer term benefits on weight control, and to develop strategies to incorporate the design principles in real foods. This research will be increasingly made in collaboration with UK food industry as the food manufacturing industry is seen as the main vehicle through which these benefits will be delivered to the individual. Timescale: The research is likely to generate benefits to industry in the form of new food products with proven effects on satiety and weight control over the next 5 to 10 years. Because the aim of this strategy is to moderate long term weight gain, the benefits to the population may not be seen for a further 10 or 20 years.