Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity-Associated Diseases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Insulin sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure.
研究概览
简要总结
The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals.
Both groups will have:
- screening visit
- imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging [MRI] and magnetic resonance spectroscopy [MRS] scans)
- Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies Participants with obesity will complete meetings with study team members for a weight loss intervention to achieve a 10% body weight loss.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age: ≥18 but ≤70 years
- •not pregnant or breastfeeding
- •weight stable and sedentary before enrollment
- •no use tobacco products, excessive amounts of alcohol, or dietary supplements, or medications known to or suspected to affect glucose and lipid metabolism (aside from certain medications used to treat diabetes in the metabolically abnormal obesity [MAO]-Type 2 Diabetes group)
- •no evidence of significant organ system dysfunction or disease (e.g. chronic severe kidney disease, cancer)
- •participants must fulfil all of the following group-specific inclusion criteria below:
- •Lean group:
- •Body mass index (BMI) ≥18.5 but <25.0 kg/m2
- •Intrahepatic triglyceride (IHTG) content <5%
- •fasting blood glucose concentration: <100 mg/dl
- •blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
- •Hemoglobin A1C (HbA1c) <5.7 %
- •Metabolically normal obesity (MNO) group:
- •BMI ≥30.0 but <45.0 kg/m2
- •IHTG content <5%
- •fasting blood glucose concentration: <100 mg/dl
- •blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
- •HbA1c <5.7 %
- •Metabolically abnormal obesity (MAO)-insulin resistance and non-alcoholic fatty liver disease (NAFLD) group:
- •BMI ≥30.0 but <45.0 kg/m2
- •IHTG content >7.5%
- •fasting blood glucose concentration: ≥100 but <126 mg/dl
- •blood glucose concentration 2 h after a 75 g oral glucose challenge: ≥140 but <200 mg/dl
- •HbA1c: ≥5.7 but <6.4 %
- •MAO-type 2 diabetes group:
- •BMI ≥30.0 but <45.0 kg/m2
- •clinical diagnosis of type 2 diabetes or fasting blood glucose concentration >126 mg/dl or blood glucose concentration 2 h after a 75 g oral glucose challenge>200 mg/dl or HbA1c >6.4 % without medication if not diagnosed and medically treated for diabetes
排除标准
- •- Individuals that do not meet all inclusion Criterion
研究组 & 干预措施
Individuals with Type 2 Diabetes Mellitus
Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.
干预措施: Dietary consultation weight loss intervention (Other)
Lean Individuals
No intervention will be administered.
Metabolically abnormal obese Individuals (obesity with normoglycemia and abnormal liver fat content)
Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.
干预措施: Dietary consultation weight loss intervention (Other)
Metabolically normal obese Individuals (obesity with normoglycemia and normal liver fat content)
Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.
干预措施: Dietary consultation weight loss intervention (Other)
结局指标
主要结局
Insulin sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure.
时间窗: up to 6 months after the intervention
24-hour plasma glucose concentration
时间窗: up to 6 months after the intervention
Macrophage isolation in adipose tissue biopsy
时间窗: up to 6 months after the intervention
macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)
Macrophage isolation in skeletal muscle tissue
时间窗: up to 6 months after the intervention
macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)
次要结局
未报告次要终点
研究者
Bettina Mittendorfer
Senior Associate Dean for Research; Professor, Medicine & Nutrition; NextGen Director of Clinical and Translational Sciences Unit
University of Missouri-Columbia