Effects of High-Intensity Interval Training in Adolescents with NAFLD

项目总结 非酒精性脂肪性肝病，特征是肝内甘油三酯升高(IHTG≥5% 肝脏体积)积聚，与肥胖、胰岛素抵抗(IR)和减少密切相关 心肺健康。未经治疗的非酒精性脂肪肝可导致进行性肝损害。易感因素 导致不良结果的原因没有得到很好的刻画。尽管IR被认为是发展的核心 NAFLD，并不是所有IR的受试者都会发生NAFLD。然而，IR的程度与IHTG呈正相关 患有非酒精性脂肪肝的人。独立于IR的心肺健康水平与IHTG呈负相关。 此外，患有非酒精性脂肪性肝病的儿童和成人有不良的循环血脂谱和升高的标记物。 炎症，这使他们面临未来心脏代谢并发症的风险。使用磁共振 成像，我们显示40%的肥胖儿童已经进入了临床体重管理 方案有不同程度的IHTG的NAFLD。在这个队列中，患有NAFLD的儿童有更高的HOMA-IR 通过连续跑步机分级评估的值(IR的替代标记物)和较低的健康水平 协议。尽管非酒精性脂肪肝的发病率和不良后果很高，但目前还没有得到批准的 以药物治疗为主。临床指南建议通过改变生活方式来减肥，尽管 这对大多数人来说并不容易实现和维持。最近的研究表明，单靠锻炼就能有效地 降低青少年的IHTG和IR，即使在体重没有明显下降的情况下也是如此。受益者 运动对NAFLD的影响也可能与IR无关。对NAFLD儿童的研究很少，而且 运动如何改善非酒精性脂肪肝仍是个谜。根据现有文献和我们自己的试验数据， 我们假设，运动导致NAFLD儿童的IHTG下降将是正相关的 随着体能的增加和IR水平的下降。在这里，我们建议进行为期4周的高强度间歇训练 (HIIT)干预与不锻炼对患有NAFLD的青少年的影响。作为一种实用和节省时间的方案，HIIT是 一种耐受性良好的运动策略，具有显著的新陈代谢益处。我们的长期目标是确定 运动是否有益于治疗儿童非酒精性脂肪性肝病，如果是的话，确定(I) 有积极反应的参与者以及(Ii)与发展和 非酒精性脂肪肝的进展(即胰岛素抵抗等)而且，通过这种运动可以改善非酒精性脂肪肝。调查结果： 这项研究将告知临床提供者使用HIIT作为治疗青少年NAFLD的一种方式，并 相关发病率，并为探索分子途径的机制研究提供初步数据 与NAFLD的发病机制有关。

PROJECT SUMMARY Non-alcoholic fatty liver disease (NAFLD), characterized by increased intrahepatic triglyceride (IHTG ≥5% of liver volume) accumulation, is strongly associated with obesity, insulin resistance (IR), and decreased cardiorespiratory fitness. Untreated NAFLD can lead to progressive hepatic damage. Predisposing factors leading to poor outcomes are not well-characterized. Although IR is thought to be central to the development of NAFLD, not all subjects with IR develop NAFLD. However, the degree of IR positively associates with IHTG in those with NAFLD. Cardiopulmonary fitness level, independent of IR, negatively associates with IHTG. Additionally, children and adults with NAFLD have unfavorable circulating lipid profiles and elevated markers of inflammation, which put them at risk for future cardiometabolic complications. Using magnetic resonance imaging, we showed that 40% of children with obesity who have entered a clinical weight management program had NAFLD with varying degrees of IHTG. Children with NAFLD, in this cohort, had higher HOMA-IR values (a surrogate marker for IR) and lower fitness levels as assessed by continuous treadmill graded protocol. Despite the high prevalence and adverse outcomes of NAFLD, there is no approved pharmacotherapy for treatment. Clinical guidelines recommend weight loss via lifestyle modifications, although this is not easy for most to achieve and sustain. Recent studies demonstrate that exercise alone can effectively decrease IHTG and IR in adolescents, even in the absence of significant weight reduction. The beneficial effects of exercise in NAFLD could also be independent of IR. Studies in children with NAFLD are scarce, and how exercise improves NAFLD remain elusive. Based on available literature and our own pilot data, we hypothesize that an exercise-driven decrease in IHTG in children with NAFLD will be positively associated with increase in fitness and decrease in IR levels. Here we propose a 4-week high-intensity interval training (HIIT) intervention vs. no exercise in adolescents with NAFLD. As a practical and time-saving regimen, HIIT is a well-tolerated exercise strategy with significant metabolic benefits. Our long term goal is to determine whether exercise is beneficial for treating pediatric NAFLD and, if so, to identify (i) the characteristics of the participants with a positive response and (ii) the mechanistic pathways implicated in the development and progression of NAFLD (i.e., insulin resistance, etc.) and, by which exercise improves NAFLD. The findings of this study will inform clinical providers in the use of HIIT as a modality to treat adolescent NAFLD and associated morbidities, and produce preliminary data for mechanistic studies to probe molecular pathways implicated in the pathogenesis of NAFLD.