IL-6 Regulation of Substrate Metabolism and Influence of Obesity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Lipolytic rate
研究概览
简要总结
The aim of the study is to investigate the effects of blocking IL-6 signaling with tocilizumab on lipid, glucose and protein metabolism during rest and exercise in healthy and obese humans.
Interleukin-6 is a molecule produced by a variety of cells and impacts on energy metabolism during fasting and fed conditions. Systemic IL-6 levels are low but increase acutely in response to fasting, exercise and infection, and also chronically in response to obesity and other conditions of lowgrade inflammation.Our recent human intervention study showed that IL-6 receptor blockade prevents exercise training from reducing visceral fat mass.
Whether IL-6 receptor blockade directly regulates lipolysis and/or lipid oxidation in humans is however unclear. Therefore, this study will be performed to investigate the physiological role of IL-6 on lipid, glucose and protein metabolism in humans.
详细描述
The aim of the study is to assess changes in substrate kinetics, that is, lipolytic rate, rate of appearance and disappearance of free fatty acids, fatty acid oxidation, glucose rate of appearance and disappearance and protein synthesis and degradation during rest and exercise with and without IL-6 receptor blockade. We will assess the acute effects of blocking IL-6 as well as the long-term consequences of IL-6 receptor blockade on all the above parameters.
Overall, we hypothesize that blocking IL-6 changes substrate kinetics. More specifically we hypothesize that blocking IL-6 reduces the appearance of free fatty acids, reduces the lipolytic rate and lipid oxidation. We hypothesize that the consequences of blocking IL-6 will be observed during resting and exercising conditions and both immediately and longterm after IL-6 receptor blockade. We hypothesize that IL-6 receptor blockade results in an increased respiratory exchange ratio (RER) and thus increased reliance on glucose as substrate.
In this study 10 healthy males and 10 obese males will be included. Subjects will be infused with saline on 2 of the study days and tocilizumab on 1 of the study days.
Isotope dilution techniques with [6,6-2H2]Glucose, [1,1,2,3,3-D5]glycerol, K-[U-13C16]palmitate, L-[ring-D5]phenylalanine, L-[D2]tyrosine will be applied to assess lipid, glucose and protein kinetics. Respiratory exchange ratio will be measured by indirect calorimetry. The BORG scale will be used to assess the perceived exertion during exercise.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Only subjects will be masked regarding order of saline and tocilizumab infusion.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •BMI < 18 and > 25 kg/m2 or ≥ 30 and ≤ 40 kg/m2
- •Healthy (based on screening)
排除标准
- •Severe thyroid or heart disease
- •inflammatory diseases
- •current infection
- •liver disease
- •kidney disease
- •immunosuppressive disease
- •corticosteroid use
- •regular NSAID usage
- •aspirin use >100 mg/d
- •history of carcinoma
- •history of tuberculosis
- •neutropenia
- •low platelets
- •bleeding disorders
- •obstructive pulmonary disease
研究组 & 干预措施
Saline infusion
Subjects will be infused with saline (placebo) on study day 1
干预措施: Saline 0.9% (Drug)
Tocilizumab infusion
Subjects will be infused with tocilizumab on study day 2
干预措施: Tocilizumab infusion (Drug)
Saline infusion under tocilizumab influence
Subjects will be infused withsaline (but still under the influence of tocilizumab) on study day 3
干预措施: Saline 0.9% (Drug)
结局指标
主要结局
Lipolytic rate
时间窗: 0-28 days
Rate of appearance and disappearance of glycerol and palmitate, fatty acid oxidation during rest and exercise in the presence of tocilizumab as compared to placebo
次要结局
- Noradrenaline(0-28 days)
- Protein metabolism(0-28 days)
- Perceived exhaustion during exercise(0-28 days)
- C-peptide(0-28 days)
- Glucagon(0-28 days)
- Adrenaline(0-28 days)
- Glucose kinetics(0-28 days)
- Triglycerides(0-28 days)
- Respiratory exchange ratio (RER)(0-28 days)
- Glucose(0-28 days)
- Insulin(0-28 days)
- Free fatty acids(0-28 days)
- Cortisol(0-28 days)
- Interleukin 6(0-28 days)
研究者
Helga Ellingsgaard
Group leader
Rigshospitalet, Denmark