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

高脂肪与高糖饮食对肝脏脂肪积累和代谢的影响

• 批准号: BB/N005600/1
• 负责人: Leanne Hodson
• 金额: $ 22.62万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN005600%2F1
• 关键词: effect; fat; vs; sugar; diet

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.

人们经常对饮食感到困惑，并问自己这样的问题：只要我不增加体重，吃太多高脂肪或高糖的食物真的有关系吗？饱和脂肪真的不像最近新闻报道的那样对我的健康有害吗？糖有什么不好的？水果含有糖分，我想我们都应该多吃水果。或者仅仅是我在食物中添加的糖对我有害？有人提出，我们吃的食物类型可能会在改变肝脏的工作方式方面发挥作用。在健康状态下，肝脏可以被认为是一台精干的、卑鄙的新陈代谢机器，但如果肝脏开始充满脂肪(称为非酒精性脂肪性肝病或NAFLD)，可能会使我们更有可能患心脏病或糖尿病。脂肪开始在肝脏堆积的原因尚不清楚，但所吃的食物的数量和类型可能都起到了重要作用。关于肝脏如何变胖，有各种不同的理论。有人建议，摄入大量脂肪，特别是饱和脂肪，会增加肝脏中的脂肪量。也有人认为，食用富含添加糖(称为非牛奶外源性糖或NMES)的饮食，如糖果和软饮料中的添加糖，也会增加肝脏中的脂肪量。然而，大多数关于饮食脂肪或糖对肝脏脂肪影响的研究都给志愿者提供了过多的卡路里。过多的卡路里，无论是来自脂肪还是糖，都被证明会增加肝脏脂肪。因此，我们想看看高脂肪或高糖饮食对肝功能的影响。我们将通过让健康、超重的男性吃两种实验饮食来研究饮食对肝脏脂肪积累和代谢的影响。这些饮食不会有过量的卡路里，但会有很大的不同。其中一种饮食将是高脂肪的，特别是饱和脂肪，但低NMES糖。另一种饮食将是低脂肪但高糖的，特别是NMES。参与者将在四周的时间里吃其中一种饮食，然后再吃八周的常规饮食，然后再吃四周的另一种饮食。这些男性饮食的顺序将被随机选择。我们将使用一种称为磁共振成像(MRI)扫描的非侵入性、高度专业化的技术来测量它们肝脏中的脂肪量，在扫描中将拍摄肝脏的照片，并测量水分和脂肪的数量。每个受试者总共将接受四次核磁共振扫描；一次是在他们开始每种实验性饮食之前，另一次是在每种饮食开始四周后进行另一次。我们还将在参与者食用实验饮食之前和之后采集他们的血液样本，以测量血脂和血糖水平的变化。实验饮食可能对肝脏脂肪代谢有不同的影响，这些变化可能只有在一系列代谢事件发生时才能观察到，例如在进餐后。为了测试实验饮食是否改变了肝脏脂肪代谢，我们将在每四周的实验饮食结束时详细调查这一点。我们将使用特殊标记的分子(稳定同位素)来实现这一点，这些分子没有放射性，并被混合到标准的测试餐中。这将是第一批比较两种实验饮食对肝脏脂肪积累和代谢影响的研究之一，这两种饮食的卡路里相似，但脂肪和糖分的量非常不同。这项工作的发现将有助于为未来制定可能在预防和治疗脂肪肝方面发挥作用的营养指南提供有价值的信息。这一点很重要，因为目前对饱和脂肪和NMES在预防和治疗疾病中的作用有很大的混淆。

项目成果

MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies.

• DOI: 10.1016/j.metabol.2023.155563
• 发表时间: 2023-07
• 期刊: METABOLISM-CLINICAL AND EXPERIMENTAL
• 影响因子: 9.8
• 作者: Nagarajan, Shilpa R.;Livingstone, Eilidh J.;Monfeuga, Thomas;Lewis, Lara C.;Ali, Shahul Hameed Liyakath;Chandran, Anandhakumar;Dearlove, David J.;Neville, Matt J.;Chen, Lingyan;Maroteau, Cyrielle;Ruby, Maxwell A.;Hodson, Leanne
• 通讯作者: Hodson, Leanne

Report of a member-led meeting: how stable isotope techniques can enhance human nutrition research

成员主导的会议报告：稳定同位素技术如何加强人类营养研究

• DOI: 10.1017/s0029665120007016
• 发表时间: 2020
• 期刊: Proceedings of the Nutrition Society
• 影响因子: 7
• 作者: Fielding B

Determining the temporal, dose, and composition effects of nutritional substrates in an in vitro model of intrahepatocellular triglyceride accumulation.

• DOI: 10.14814/phy2.15463
• 发表时间: 2022-10
• 期刊: Physiological reports
• 影响因子: 2.5

Using total plasma triacylglycerol to assess hepatic de novo lipogenesis as an alternative to VLDL triacylglycerol.

使用总血浆三酰甘油来评估肝脏从头脂肪生成，作为 VLDL 三酰甘油的替代品。

• DOI: 10.1080/03009734.2020.1739789
• 发表时间: 2020
• 期刊: Upsala journal of medical sciences
• 影响因子: 3.4
• 作者: Hodson L

An optimised protocol for the investigation of insulin signalling in a human cell culture model of adipogenesis.

• DOI: 10.1080/21623945.2023.2179339
• 发表时间: 2023-12
• 期刊: ADIPOCYTE
• 影响因子: 3.3
• 作者: Gamwell, Jonathan M.;Paphiti, Keanu;Hodson, Leanne;Karpe, Fredrik;Pinnick, Katherine E.;Todorcevic, Marijana
• 通讯作者: Todorcevic, Marijana