Diacylglycerols and Insulin Action in Skeletal Muscle Upon Caloric Restriction
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- UPLC-ESI MS/MS profiling of lipd extracts from muscle biopsies to evaluate effects of gastric bypass induced-caloric restriction on diacylglycerol molecular species accumulation.
研究概览
简要总结
Research has shown that fat stored within muscles affects the muscle's sensitivity to insulin and ability to handle blood glucose. The purpose of this study is to examine the effects of weight loss surgery-induced caloric restriction on the accumulation and types of fats within skeletal muscle, as well as the effects of such caloric restriction on insulin sensitivity and inflammatory responses in skeletal muscle. The investigator proposes that caloric restriction will result in decreases in diacylglycerols enriched with saturated fat and increases in diacylglycerols enriched with monounsaturated fats.
详细描述
We hypothesize that in a setting of surgically-induced weight loss decrements in select DAGs result in improved glucose utilization, altered insulin signaling and decreased inflammatory responses. We propose to examine the impact of molecular DAG species accumulation on glucose utilization, insulin signaling and inflammation in skeletal muscle from morbidly obese subjects before/after 10% weight loss facilitated by Roux-en-Y Gastric Bypass (RYGB). We will compare these results to those from a control, normal weight cohort
The detected differences in DAG molecular species, insulin action, inflammatory responses between normal and obese subjects (before/after weight loss) will emphasize pathways coordinately altered as a consequence of adiposity and RYGB surgery. The primary endpoints for this study will be: Insulin sensitivity (glucose Rd, insulin levels, DAG mass, DAG species amounts).Secondary endpoints will be: FFA levels, inflammatory cytokine production, and insulin signaling in skeletal muscle.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •For Normal Weight Subjects:
- •Age 21-65 years
- •BMI of 21 to 27 kg/m2
- •Normal glucose tolerance as determined by OGTT on day of screening
- •No family history of diabetes
- •For Morbidly Obese Subjects:
- •Age 21-65 years
- •BMI of 30 to 65 kg/m2
- •Scheduled for Roux-en-Y gastric bypass at Vanderbilt Medical Center
- •Insulin resistant as determined by OGTT on day of screening
排除标准
- •(for all subjects):
- •Clinically significant heart disease
- •Clinically significant hepatic or renal disease
- •Pregnancy
- •Breastfeeding
- •Any abnormality that would preclude safe completion of study
- •Use of statins
- •Use of thiazide or furosemide diuretics, beta blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless subject has been on stable dose of such medications for the past 3 months before entering the study
结局指标
主要结局
UPLC-ESI MS/MS profiling of lipd extracts from muscle biopsies to evaluate effects of gastric bypass induced-caloric restriction on diacylglycerol molecular species accumulation.
时间窗: 1 year
Diacylglycerol content and composition
时间窗: after 10% body weight loss
Muscle lipid will be analyzed by LC-MS/MS
次要结局
- To evaluate the effects of gastric bypass induced-caloric restriction on skeletal muscle insulin action via a hyperinsulinemic-euglycemic clamp and profiling markers of insulin signaling.(1 year)
- To evaluate the effects of gastric bypass induced-caloric restriction on lipid-mediated inflammatory responses by profiling cytokines and free fatty acids in blood and inflammation markers in skeletal muscle biopsies.(1 year)
- Insulin sensitivity and glucose disposal(after 10% body weight loss)
- Muscle gene expression(after 10% body weight loss)
研究者
Charles R. Flynn
Assistant Professor
Vanderbilt University