Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Net hepatic phospholipid production
研究概览
简要总结
The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. The investigators plan to examine this hypothesis in a well-characterized cohort of obese subjects that are scheduled for bariatric surgery. Methyl-D9-choline chloride will be infused before and after a 2-week high fructose or glucose feeding to determine the biosynthesis and kinetics of secretory lipoprotein phospholipids. It is proposed that phospholipid metabolism play an important role in the pathogenesis or etiology of fatty liver in non-alcoholic conditions through mechanisms that invoke ER and oxidative stress responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Ambulatory females age 30-60 years old
- •Women of all ethnic groups
- •BMI≥35 kg/m2
- •Approval for Roux-en-Y gastric bypass or sleeve gastrectomy.
排除标准
- •Smoking >7 cigarettes per day
- •Previous malabsorptive or restrictive intestinal surgery
- •Pregnant or breastfeeding
- •Recent history of neoplasia (<5 years ago)
- •Malabsorptive syndromes
- •Inflammatory intestinal disease
- •Patients with established organ dysfunction
- •Diagnosis of type 1 or type 2 diabetes mellitus or current use of anti-diabetic medication (last 30 days; last 60days for thiazolidinediones)
- •Diagnosed hyperbetalipoproteinemia or hypobetalipoproteinemia
- •Patients on cholesterol lowering medicines
- •Vegan diet
- •Hepatic fat content <10% by MRI
- •Inability to comply with study protocol such as unable to make study visits or be available daily for phone contact
- •Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, chronic back pain limiting ability to lay flat, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning.
研究组 & 干预措施
Fructose
Participants will receive fructose (3g/kg/day) for 2 weeks.
干预措施: methyl-D9-choline (Drug)
Glucose
Participants will receive glucose (3g/kg/day) for 2 weeks.
干预措施: methyl-D9-choline (Drug)
结局指标
主要结局
Net hepatic phospholipid production
时间窗: Baseline and 2 weeks
Net hepatic phospholipid production will be determined using \[11C\]choline dynamic Positron Emission Tomography (PET) before and after high fructose feeding for two weeks. A similar group of control obese subjects will undergo the same procedures before and after two weeks isocaloric glucose feeding.
次要结局
- Kinetics of secretory lipoprotein phospholipids(Baseline and 2 weeks)
研究者
Charles R. Flynn
Assistant Professor
Vanderbilt University