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The effect of a high fat vs high sugar diet on liver fat accumulation and metabolism

Reference	BB/N005600/1
Principal Investigator / Supervisor	Professor Leanne Hodson
Co-Investigators / Co-Supervisors
Institution	University of Oxford
Department	RDM OCDEM
Funding type	Research
Value (£)	177,535
Status	Completed
Type	Research Grant
Start date	01/09/2016
End date	28/02/2019
Duration	30 months

Abstract

The proposed work aims to compare the effect of two experimental isocaloric diets with notably different amounts of fat (specifically saturated fat) and carbohydrate (specifically non-milk extrinsic sugars (NMES), also called free or added sugars), on liver fat accumulation and metabolism in healthy, overweight men. Sixteen men will consume the diets 1) a high-fat (specifically saturated fat) low NMES diet and, 2) a low-fat, high NMES diet in random order for four weeks, with an eight week washout period in between, before crossing over to the alternate diet for four weeks. Liver fat content will be measured, by MRS prior to starting the experimental diets and then four weeks after consuming the diet. Fasting blood samples will also be taken at this time. As the diets may differ in their effect on intrahepatic fatty acid partitioning and these will only be observed once a cascade of metabolic events occur, such as after consumption of a mixed meal, participants will undergo postprandial study day at the end of each dietary phase. On the postprandial study day stable-isotope tracer methodologies will be utilised to probe the effect of the dietary regime on intrahepatic fatty acid partitioning. Blood and breath samples will be taken prior to and then regularly after consumption of a standard test meal, for 6 hours. This will be one of the first studies to compare the effects of isocaloric diets enriched with either saturated fat or NMES on liver fat content and metabolism. By undertaking a postprandial study day at the end of the each dietary regime, key mechanisms that play a pivotal role in development of fatty liver disease and effect risk of CVD, will be elucidated. The findings will aid in underpinning future nutritional guidelines that may play a role in preventing and treating NAFLD. This is of importance as there is much confusion over the role of macronutrients in the prevention and treatment of non-communicable diseases, including NAFLD.

Summary

People are often confused about diet and ask themselves questions such as: Does it really matter if I eat too many foods high in fat or high in sugar, as long as I don't put on weight? Is it true that saturated fat isn't bad for my health, as reported in the news recently? What is so bad about sugar? Fruit contains sugar, and I thought we should all eat more fruit. Or is it just the sugar that I add to my food that is bad for me? It has been suggested that the type of food we eat may play a role in changing the way the liver works. In health, the liver can be considered a lean, mean, metabolic machine, but if the liver starts to become filled with fat (something called non-alcoholic fatty liver disease or NAFLD) it can make us more at risk of getting heart disease or diabetes. Why fat starts to build up in the liver isn't clear, but both the amount and type of food eaten may play an important role. There are various theories about how the liver becomes fatty. It has been suggested that eating lots of fat, especially saturated fat, can increase the amount of fat within the liver. It is also thought that consuming a diet rich in added sugars (known as non-milk extrinsic sugars or NMES), such as those found in sweets and soft drinks, also increases the amount of fat in the liver. However, most of the studies that have looked at the effects of dietary fat or sugar on liver fat have fed the volunteers excess calories. Excess calories, whether from fat or sugar, have been shown to increase liver fat. Therefore, we would like to look at the effects of diets rich in fat or rich in sugar, without excess calories, on liver function. We will study the effect of diet on liver fat accumulation and metabolism by asking healthy, overweight men to eat two experimental diets. These diets will not have excess calories but will be very different. One of the diets will be high in fat, especially saturated fat but low in NMES sugar. The other diet will be low in fat but high in sugar, especially NMES. Participants will eat one of the diets for a period of four weeks and then eat their usual diet for eight weeks before eating the alternate diet for a further four weeks. The order in which the men eat each diet will be chosen at random. We will measure the amount of fat in their liver using a non-invasive, highly specialised technique known as magnetic resonance imaging (MRI) scans, where pictures will be taken of the liver and the amount of water and fat measured. Each subject will have a total of four MRI scans; one before they start each experimental diet and then another after four weeks of eating each diet. We will also take blood samples from participants before and then after they have consumed the experimental diets to measure changes in blood fat and sugar levels. The experimental diets may have different effects on liver fat metabolism and these changes may only be observed when a cascade of metabolic events occur, such as after consumption of a meal. To test if the experimental diets have changed liver fat metabolism, we will investigate this in detail at the end of each four week experimental diet. We will do this using specially labelled molecules (stable-isotopes), which are not radioactive and are mixed into a standard test meal. This will be one of the first studies to compare the effects of two experimental diets that have similar calories but very different amounts of fat and sugar on liver fat accumulation and metabolism. The findings from this work will help to provide valuable information for the development of future nutritional guidelines that may play a role in preventing and treating fatty liver disease. This is of importance as there is currently much confusion over the role of saturated fat and NMES in the prevention and treatment of diseases.

Impact Summary

This proposal will further understanding of how dietary sugars and fats impact on liver fat accumulation and metabolism, providing much needed evidence in an emerging area of concern. The British Liver Trust states that liver disease is the only major cause of death that is still increasing year-on-year and is the fifth 'big killer' in England & Wales, after heart disease, cancer, stroke and respiratory disease. This increasing prevalence is having not only a huge impact on the lives of sufferers, but also results in a substantial cost to the National Health Service. In 2011, the direct healthcare costs of liver disease were estimated to be in excess of £0.5bn per annum. The present study addresses the accumulation of liver fat, a common condition termed non-alcoholic fatty liver disease (NAFLD). This has been estimated to affect over 30% of adults and can be a precursor to more serious forms of liver disease such as non-alcoholic steatohepatitis, which is a risk factor for cirrhosis, liver failure and more rarely, liver cancer. NAFLD is often associated with obesity and several studies have now shown the level of fat in the liver to be markedly reduced by weight loss and this remains a cornerstone for the current treatment and management of the disease. What is less clear is the role of different dietary components, and there is a real paucity of evidence of how fat accumulates in the liver. Policy makers and health professionals work together to provide the public with advice on disease prevention and health practitioners need the best information available to aid the effective treatment of patients. The findings from the current study will be shared with these important audiences via presentations at policy maker and health professional seminars and briefing notes, which Sugar Nutrition UK send to MPs and peers along with articles in the relevant professional press. The results of the proposed research will also be of relevance to the wider medical and pharmaceutical industry as there is a paucity of research investigating the mechanisms responsible for the accumulation of fat in the liver, with very few pharmaceutical strategies recommended to help address the issue. The information from this study may therefore aid the development of other treatment options. In addition to the academic beneficiaries described in the previous section, this research will be of benefit to policy makers, the food industry, and the general population. Initiatives such as the Responsibility Deal rely on evidence-based dietary guidelines and policies to ensure that the food industry make the optimum changes to improve the health benefits of the products they manufacturer. More evidence is therefore needed on the impact of specific constituents of foods on relevant health outcomes. It is also vital that consumers have access to the best available evidence to help them make informed choices as to which foods and products to consume. In particular, the recent media coverage of the controversy on the role of saturated fats and sugars in health causes real difficulty for the consumer to make these decisions. It is therefore vital that research directly addresses these controversies to provide evidence to clarify the impact of dietary components on health. Press releases of the study results, along with the study authors providing journalists with briefings and interviews will encourage accurate reporting to the public, with clear take home messages. Researchers will also explore the opportunity to speak to interested patient groups, where dietary advice may be advantageous.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Ageing, Diet and Health
Research Priority	X – Research Priority information not available
Research Initiative	LINK: Responsive Mode [2010-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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