Effect of High-Intensity Interval Training in Adolescents with Hepatosteatosis

高强度间歇训练对青少年肝脂肪变性的影响

• 批准号: 10260366
• 负责人: Emir Tas
• 金额: $ 22.85万
• 依托单位: ARKANSAS CHILDREN'S HOSPITAL RES INST
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260366
• 关键词: Adolescent; Adult; Arkansas; Benign; Characteristics; Child; Cirrhosis; Clinical; Clinical Research; Data; Diagnosis; Disease Outcome; Disease Progression; Ethnic Origin; Exercise; FGF21 gene; Fatty Liver; Fatty acid glycerol esters; Glucose; Health; Hepatic; High Prevalence; Hispanics; Infiltration; Insulin; Insulin Resistance; Interval training; Lead; Life Style Modification; Lipids; Liver; MRI Scans; Magnetic Resonance Imaging; Mediating; Metabolic; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Paris, France; Participant; Pathway interactions; Pediatric Hospitals; Race; Resistance; Risk Factors; Serum; Time; Weight maintenance regimen; adiponectin; adult obesity; analog; chronic liver disease; clinically relevant; cohort; diet and exercise; ethnic difference; exercise regimen; fatty acid oxidation; fibroblast growth factor 21; improved; lipid biosynthesis; lipid metabolism; liver injury; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel marker; obesity in children; obesity prevention; programs; racial and ethnic; response; tool; treatment response

Non-alcoholic fatty liver disease (NAFLD) Is the Ieading cause of chronic liver disease in Children and adults and is strongly associated with obesity and insulin resistance. NAFLD is defined by fatty infiltration of :: 5% of liver volume. Once considered a benign condition, untreated NAFLD can lead to progressive hepatic damage, non-alcoholic steatohepatitis (NASH), and eventually cirrhosis. Hispanics have the highest prevalence of NAFLD, although the reasons for racial/ethnic differences are mostly unknown. Recent studies showed that liver fat percent is an independent risk factor for disease progression. There is a lack of clinically accessible and inexpensive tools to diagnose and monitor the liver fat changes over time. Jsing magnetic resonance imaging, we have demonstrated that 40% of children with obesity who have entered a clinical weight management program at the Arkansas Children's Hospital had NAFLD with varying degrees of liver fat percent at baseline. Children with NAFLD, in this cohort, had higher circulating Fibroblast Growth Factor (FGF)-21 and lower adiponectin concentrations compared to children without NAFLD. Furthermore, after 6-months of unsupervised lifestyle modifications and repeated liver MRI scans, % change in liver fat percent was significantly correlated with % change in FGF21 to Adiponectin Ratio :FAR) in those with NAFLD at baseline. This finding is clinically relevant because FAR may be an Adjunct tool to monitor liver fat content in response to treatments such as diet and exercise. FGF21 is a hepatokine md metabolic regulator that improves the whole body and hepatic lipid metabolism (i.e., FGF-21 induces 1epatic fatty acid oxidation and inhibits de novo lipogenesis, thus favoring decreased hepatic lipid content). nterestingly, obesity is characterized by an FGF21 resistance state. Some of the positive effects of exercise on metabolic health are hypothesized to be related to the FGF21-adiponectin axis. Adults with obesity and type 2 diabetes who were treated with exogenous FGF21 analogs had an elevation in their serum concentrations of adiponectin, suggesting that adiponectin mediates some of the beneficial effects of =-GF21. We hypothesize that the HIIT-driven improvements in hepatic steatosis will be associated with the changes in FGF21-adiponectin and insulin resistance at different degrees among ethnicities. The liver fat content will be quantified, and changes will be monitored via Fibroscan® (Echosens, Paris). The long-term oal is to determine whether HIIT is beneficial for treating NAFLD in adolescents and, if so, to identify (i) the characteristics of the participants with a positive response and (ii) the mechanistic pathways including FGF21-adiponectin and insulin-glucose axis by which HIIT improves NAFLD. Preliminary data generated 'rom this translational clinical study will guide studies to compare the effects of different exercise regimens md to examine if there are differential effects of race/ethnicity on exercise-driven changes in insulin resistance, FGF21-adiponectin axis, other novel biomarkers, and NAFLD outcomes.

非酒精性脂肪肝疾病（NAFLD）是慢性肝脏疾病的原因 儿童和成人，与肥胖和胰岛素抵抗密切相关。 nafld由脂肪定义 :: 5％的肝脏浸润。一旦被视为良性条件，未经处理的NAFLD可能会导致进步 肝损伤，非酒精性脂肪性肝炎（NASH）以及最终的肝硬化。西班牙裔有 NAFLD的最高患病率，尽管种族/种族差异的原因大多是未知的。 最近的研究表明，肝脂肪百分比是疾病进展的独立危险因素。 缺乏临床上且廉价的工具来诊断和监测肝脏脂肪的变化 随着时间的推移。 jsing磁共振成像，我们证明了40％的肥胖儿童 在阿肯色州儿童医院进入临床体重管理计划的人与NAFLD一起 基线时肝脂肪百分比的不同程度。 Nafld的孩子，在这个队列中， 与没有的儿童相比 nafld。此外，经过6个月的无监督生活方式修改并重复进行肝脏MRI 扫描，肝脏脂肪百分比变化的％与FGF21变化的百分比显着相关 比率：在基线时具有NAFLD的人。这一发现在临床上是相关的，因为可能是 根据饮食和运动等治疗方法监测肝脏脂肪含量的辅助工具。 FGF21是a 肝素MD代谢调节剂，可改善整个身体和肝脂质代谢（即， FGF-21诱导1epati脂肪酸氧化并抑制从头脂肪生成，因此有利于 肝脂质含量降低）。令人难以置信的是，肥胖的特征是FGF21抗性 状态。假设运动对代谢健康的一些积极影响与FGF21-磷胶蛋白轴有关。成年人 用外源FGF21类似物治疗的肥胖和2型糖尿病的升高 脂联素的血清浓度，表明脂联素介导 = -GF21。我们假设由HIIT驱动的肝脂肪变性改善将与 随着族裔之间不同程度的FGF21-辅导蛋白和胰岛素抵抗的变化。这 将量化肝脂肪含量，并通过Fibroscan®（Echosens，Paris）监测变化。这 长期OAL是确定HIIT是否有益于在青少年中治疗NAFLD以及是否有益 因此，要确定（i）具有正反应的参与者的特征，以及（ii）机械途径 HIIT改善NAFLD，包括FGF21-辅助蛋白和胰岛素 - 葡萄糖轴。初步数据 生成的'rom这本翻译的临床研究将指导研究比较 不同的运动方案医学博士检查种族/种族是否有不同的影响 运动驱动的胰岛素耐药性，FGF21-磷胶蛋白轴，其他新型生物标志物和NAFLD结果的变化。