Short-term High-fat Overnutrition Induces Insulin Resistance in White Adipose Tissue
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Whole-body insulin sensitivity and WAT insulin sensitivity
研究概览
简要总结
Type 2 diabetes is the most common metabolic disease worldwide, characterized by hyperglycemia, decreased whole body insulin sensitivity, and white adipose tissue (WAT) dysfunction. A key factor in its development is chronic overnutrition, usually with a high-fat diet (HFD), leading to disturbances of glucose and lipid metabolism. However, the mechanism of short-term HFD-induced tissue-specific insulin resistance remains poorly understood. This project aims to further unravel the underlying mechanisms of short-term HFD overnutrition-mediated WAT insulin resistance. The model described here corresponds to a randomized, single- blinded parallel-grouped trial, consisting of two interventions: a macronutrient-balanced diet and or a hypercaloric diet over three weeks in order to investigate differences in interorgan fatty acid and glucose metabolism between the studied groups. Based on recent studies, the hypothesis is that 21-day hypercaloric HFD induces WAT insulin resistance via a diacylglycerol, novel protein kinase C-insulin receptor signaling model in both fasting and insulin-stimulated states.
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 (Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 40 years
- •BMI < 29 kg/m2
- •Sport inactive (<1x /week)
- •Capacity to consent
排除标准
- •Diabetes mellitus disease
- •Acute coronary heart syndrome (myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack in the last 3 months before study participation)
- •Acute infectious disease
- •Taking blood glucose-lowering drugs
- •Diseases or drugs affecting the immune system and allergies to drugs used in the study
- •Drugs with potential metabolic effects
- •Chronic liver disease (hepatitis, gallbladder disease, elevated liver enzymes (ALT > 300 U/L))
- •Chronic inflammatory bowel diseases
- •Rheumatic diseases
- •Hyper- or hypothyroidism of the thyroid gland
- •Renal insufficiency, administration of iodine-containing contrast media in the last 2 days
- •Chronic lung diseases
- •cancerous diseases
- •Addictive diseases, psychiatric diseases
- •Pregnancy, breastfeeding
- •Shift workers
- •Anemia (Hb <12 g/dl)
- •Disorders of hemostasis
- •Regular use of antithrombotic drugs
- •Alcohol consumption, smoking
- •Conditions that do not permit an MRI examination
研究组 & 干预措施
High-fat overnutrition
Lipid overnutrition: 40% higher lipid consumption per day than required over three weeks.
干预措施: High-fat overnutrition (Behavioral)
Normocaloric macronutrient-balanced nutrition
Normocaloric, macronutrient-balanced nutrition per day over three weeks
干预措施: Normocaloric macronutrient-balanced nutrition (Behavioral)
结局指标
主要结局
Whole-body insulin sensitivity and WAT insulin sensitivity
时间窗: 3 weeks intervention period each
Hyperinsulinemica-euglycemia clamp tests with deuterated glucose to measure fasting and insulin-stimulated whole-body insulin sensitivity and measurement of the index ADIPO-IR (fasting insulin x free fatty acid concentration) before and after dietary intervention period.
次要结局
- WAT insulin signaling pathways(3 weeks intervention time)