Dietary Salt has an Unrecognized Role in Modulating Energy Intake and Metabolic Syndrome

膳食盐在调节能量摄入和代谢综合征方面的作用尚未被认识

• 批准号: 9114329
• 负责人: Richard Joseph Johnson
• 金额: $ 40.15万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9114329
• 关键词: Adipose tissue; Aldehyde Reductase; Animals; Automobile Driving; Blood; Body Weight decreased; Body fat; Brain; Caloric Restriction; Calories; Carbohydrates; Cereals; Clinical; Clinical Trials; Dairy Products; Data; Development; Diabetes Mellitus; Diet; Diet and Nutrition; Eating; Educational process of instructing; Energy Intake; Energy Metabolism; Engineering; Enzymes; Exercise; Expenditure; Fatty Liver; Fatty acid glycerol esters; Food; Food Labeling; Fructokinases; Fructose; Generations; Genes; Genetic Transcription; Glucose; Guidelines; Hepatic; Human; Hyperinsulinism; Hyperphagia; Hypothalamic structure; Individual; Insulin Resistance; Intake; Knockout Mice; L-Iditol 2-Dehydrogenase; Lead; Leptin; Leptin resistance; Link; Literature; Liver; Longitudinal Studies; Mediating; Messenger RNA; Metabolic; Metabolic syndrome; Metabolism; Micronutrients; Mus; Nutritional; Obesity; Organ; Osmolar Concentration; Overweight; Oxidative Stress; Pathogenesis; Pathway interactions; Process; Production; Proteins; Recommendation; Reporting; Research; Resistance; Risk; Role; Signal Transduction; Sodium Chloride; Sorbitol; Source; System; Testing; Up-Regulation; Uric Acid; Water; Weight Gain; bariatric surgery; base; diabetes risk; dietary salt; energy balance; feeding; fructose-1-phosphate; fruits and vegetables; high salt diet; lean body mass; lipid biosynthesis; liver development; novel; nutrition; nutritional guideline; obesity risk; polyol; prevent; public health relevance; reduced food intake; response; salt intake; sugar; transcription factor

 DESCRIPTION (provided by applicant): The classical approach to treat obesity, fatty liver and metabolic syndrome involves dietary calorie restriction, exercise, and, if necessary, bariatric surgery. Most diets focus on reducing energy intake, usually by restricting carbohydrates, proteins, and/or fat. Nutritional guidelines, such as the USDA MyPlate (food pyramid), focus on the caloric content of foods, such as proteins, grains, fruits, vegetables and dairy products. While most diets teach us how to count the calories we eat, rarely is weight loss sustained. It appears like something may be missing. In this proposal, we hypothesize that the non-caloric component of foods has an important, yet unrecognized, role in increasing the risk for obesity, fatty liver and insulin resistance. Based on our preliminary data, we propose that dietary salt, a noncaloric micronutrient present in many foods, has a role in influencing whether carbohydrates will act as simple caloric source or will initiate a metabolic system leading to fatty liver, insuln resistance, decreased leptin sensitivity, and weight gain. We hypothesize that the mechanism whereby dietary salt controls carbohydrate metabolic effects is mediated by its ability to hypertonically up-regulate and activate the aldose reductase-fructokinase system in liver, adipose tissue and brain. Aldose reductase up-regulation is mediated by the activation of the transcription factor associated to hypertonicity TonEBP/NFAT5 that stimulates the transcription of aldose reductase among other osmo-regulated genes. Activation of aldose reductase in these organs results in the generation of endogenous sorbitol and fructose from glucose. Metabolism of this endogenous fructose through fructokinase drives fat production and insulin resistance in the liver while inducing leptin release in adipose tissue and central decreased leptin sensitivity n the hypothalamus. Aim 1 will test the hypothesis that salty foods raise hepatic and blood tonicity, thereby activating TonEBP, aldose reductase and the fructokinase pathway. This activation leads to endogenous fructose production, fat accumulation and insulin resistance. Also, we will study if this process occurs in animals when salt intake is provided under isoosmolar conditions. Aim 2 will test the hypothesis that salt-induced metabolic syndrome (especially insulin resistance and fatty liver) can occur in isocaloric conditions. Also, we will tst if reduced central leptin sensitivity is an important step in the pathogenesis of salt-induced metabolic syndrome These studies may modify current views on the role of nutrition in obesity and metabolic syndrome, by revealing the importance of the non-caloric component of foods. While simple in concept, our studies could modify current scientific paradigms for nutrition and diet that could lead to changes in food labeling, nutrition and the dietary management of individuals who are overweight or obese.

 描述(由申请人提供)：治疗肥胖症、脂肪肝和代谢综合征的经典方法包括限制饮食卡路里、锻炼，如果必要的话，还可以进行减肥手术。大多数饮食侧重于减少能量摄入，通常是通过限制碳水化合物、蛋白质和/或脂肪。营养指南，如USDA我的餐盘(食物金字塔)，重点关注食物的卡路里含量，如蛋白质、谷物、水果、蔬菜和乳制品。虽然大多数饮食教会我们如何计算我们摄入的卡路里，但很少有人能持续减肥。看起来可能遗漏了什么东西。在这项提案中，我们假设食物中的非卡路里成分在增加肥胖、脂肪肝和胰岛素抵抗的风险方面具有重要的、但尚未被认识的作用。根据我们的初步数据，我们认为食盐，一种存在于许多食物中的非热量微量营养素，在影响碳水化合物是作为简单的热量来源还是将启动导致脂肪肝、胰岛素抵抗、瘦素敏感性降低和体重增加的代谢系统中发挥作用。我们假设，食盐控制碳水化合物代谢效应的机制是通过高张上调和激活肝脏、脂肪组织和大脑中的醛糖还原酶-果糖激酶系统的能力来调节的。醛糖还原酶的上调是通过激活与高张力TONEBP/NFAT5相关的转录因子来介导的，该转录因子刺激了醛糖还原酶等渗透调节基因的转录。这些器官中的醛糖还原酶的激活导致从葡萄糖中产生内源性山梨醇和果糖。这种内源性果糖通过果糖激酶代谢，促进肝脏脂肪生成和胰岛素抵抗，同时诱导脂肪组织释放瘦素，并降低下丘脑对瘦素的敏感性。目的1验证这样一种假说，即咸味食物可以增强肝脏和血液的紧张性，从而激活TONEBP、醛糖还原酶和果糖激酶途径。这种激活会导致内源性果糖的产生、脂肪积累和胰岛素抵抗。此外，我们还将研究在等渗条件下提供盐摄入量时，这一过程是否会在动物身上发生。目的2将验证盐诱导的代谢综合征(特别是胰岛素抵抗和脂肪肝)在等卡路里条件下会发生的假设。此外，如果中枢瘦素敏感性降低是盐诱导的代谢综合征发病机制中的重要一步，我们将进行TST。这些研究可能会通过揭示食物中非热量成分的重要性，改变目前关于营养在肥胖和代谢综合征中的作用的观点。虽然我们的研究在概念上很简单，但我们的研究可以修改目前的营养和饮食科学范式，这可能会导致超重或肥胖个人的食品标签、营养和饮食管理的变化。