Does a ketogenic diet impair metabolic health?

生酮饮食会损害代谢健康吗？

• 批准号: 10751471
• 负责人: Molly Rachel Gallop
• 金额: $ 6.91万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751471
• 关键词: Acute; Adherence; Affect; Automobile Driving; Beta Cell; Blood Glucose; Body Weight; Body Weight decreased; Body fat; Bolus Infusion; Carbohydrates; Cell physiology; Cholecystokinin; Chronic; Coupled; Data; Development; Diabetes Mellitus; Diet; Dietary Intervention; Eating; Energy Intake; Energy Metabolism; Epilepsy; Equilibrium; Fasting; Fatty acid glycerol esters; Feeling; Fellowship; Future; Genetic Transcription; Glucose; Glucose Intolerance; Glycosylated hemoglobin A; Goals; Health; Heart Diseases; High Fat Diet; Human; Hunger; Hyperphagia; Impairment; Insulin; Intervention; Ketone Bodies; Life; Maintenance; Mammals; Measurement; Metabolic; Mission; Monitor; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Neurons; Obese Mice; Obesity; Outcome; Participant; Patients; Peptides; Persons; Plasma; Proteins; Public Health; Reducing diet; Regulation; Reporting; Research; Risk; Rodent; Safety; Seizures; Syndrome; Testing; Therapeutic; Thinness; Weight; Weight Gain; Weight maintenance regimen; Work; blood glucose regulation; cancer type; career; design; dietary control; effective therapy; energy balance; fasting glucose; fat burning; feeding; ghrelin; glucagon-like peptide 1; glucose tolerance; improved; in vivo; innovation; insight; insulin secretion; islet; ketogenic diet; lipid biosynthesis; morphometry; obesity treatment; prevent; reduced food intake; response; transcriptomics; weight gain prevention

Project Summary Since the 1960s, a ketogenic diet (KD) has been touted as a potential treatment for diabetes and obesity. A KD is a very low carbohydrate, high fat, and moderate protein diet that has been used since the 1910s to treat epilepsy and was designed to mimic the benefits that fasting had on seizure control. Noting metabolic similarities between a KD and fasting — namely a switch from burning glucose to burning fat — a KD was hypothesized to lower fasting glucose and insulin, leading to consequent inhibition of lipogenesis, thereby favoring burning rather than storage of fat. However, the efficacy and metabolic effects of a KD have been largely underexplored. As obesity raises the risk for the development of many health conditions, including diabetes, heart disease, and multiple types of cancer, the long-term goal of this work is to develop rigorously tested and efficacious weight control therapeutics. The overall objective of this proposal is to determine whether a KD is a safe and effective treatment to control weight and blood glucose. The driving hypothesis of this proposed work is that a KD suppresses weight gain and causes weight loss but impairs glucose homeostasis. The rationale for carrying out the proposed studies is that the efficacy of a KD as a weight control diet, and the overall effects that KD has on metabolic health are unclear. Since KD is now a commonly used diet, it is critical to understand the effects of a KD on metabolic health so that we do not make health conditions worse by prescribing a KD. In humans who have obesity, some studies report greater weight loss when participants were prescribed a KD versus a control weight loss diet. However, other studies have reported that a KD produces similar effects to other weight loss diets, making the effects of KD on weight regulation unclear and necessitating further study. Conversely, while studies in both rodents and humans have shown that a KD intervention lowered fasting glucose and HbA1c, several studies have suggested that glucose tolerance is impaired on a KD. This proposed work is of crucial importance since a KD is prescribed to people who may already have diabetes or obesity, so it is imperative to understand if a KD worsens blood glucose regulation. Thus, to ascertain whether a KD is a metabolically safe and beneficial intervention for people with diabetes and/or obesity, we will elucidate the mechanisms by which a KD controls body weight (Aim 1) and establish the effects of a KD on beta cell function (Aim 2). The proposed studies are innovative as the mechanistic effects of KD on weight and blood glucose regulation have been largely under-investigated. Ultimately, these studies will determine whether a KD is a safe and effective treatment for weight control and glucose homeostasis. Furthermore, mechanistic insights gained from elucidating the effects of a KD on weight control will pave the way for the development of future weight control therapies.

项目摘要 自20世纪60年代以来，生酮饮食(KD)一直被吹捧为糖尿病和肥胖症的潜在治疗方法。A KD 是一种非常低碳水化合物、高脂肪和中等蛋白质的饮食，自1910年以来一直用于治疗 它是为了模仿禁食对控制癫痫的益处。注意到新陈代谢的相似性 在KD和禁食之间--即从燃烧葡萄糖到燃烧脂肪的转变--KD被假设为 降低空腹血糖和胰岛素，从而抑制脂肪生成，从而有利于燃烧 而不是储存脂肪。然而，KD的疗效和代谢影响在很大程度上还没有得到充分的研究。AS 肥胖增加了许多健康状况的风险，包括糖尿病、心脏病和 多种癌症，这项工作的长期目标是开发严格测试和有效的体重 控制疗法。这项建议的总体目标是确定KD是否安全有效 控制体重和血糖的治疗。这项拟议工作的驱动假说是一个KD 抑制体重增加，导致体重减轻，但损害血糖稳态。实施的理由是 建议的研究是KD作为体重控制饮食的有效性，以及KD对 新陈代谢健康状况尚不清楚。由于KD现在是一种常用的饮食，了解一种 KD关于新陈代谢健康，这样我们就不会因为开KD而使健康状况变得更糟。在人类中， 患有肥胖症，一些研究报告称，与对照组相比，服用KD的参与者体重减轻更快 减肥食谱。然而，其他研究报告称，KD与其他减肥效果相似。 饮食，使得KD对体重调节的影响尚不清楚，需要进一步研究。相反，虽然 对啮齿动物和人类的研究表明，KD干预降低了空腹血糖和HbA1c， 多项研究表明，KD患者的糖耐量受损。这项拟议的工作至关重要 重要性因为KD是给可能已经患有糖尿病或肥胖症的人开的，所以必须 了解KD是否会恶化血糖调节。因此，要确定KD是否在代谢上安全 以及对糖尿病和/或肥胖症患者的有益干预，我们将阐明 KD控制体重(目标1)，并确定KD对β细胞功能的影响(目标2)。建议数 研究是创新的，因为KD对体重和血糖调节的机制影响在很大程度上 调查不足。最终，这些研究将确定KD是否是一种安全有效的治疗方法 控制体重和血糖平衡。此外，从阐明这些影响中获得的机械论见解 关于体重控制的KD研究将为未来体重控制疗法的发展铺平道路。