Fat Metabolism and Function Altering Polymorphisms in MC3R
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Free fatty acid reflux rate measured on a high- fat diet during the hyperinsulinemic state
研究概览
简要总结
Background:
- Melanocortin receptors are proteins in the body that help send messages between body systems. One such receptor, the melanocortin 3 receptor (MC3R), is important for regulating body weight. Differences in MC3R can affect fat metabolism - or how the body handles fat. Some people who have changes in the MC3R genetic code are heavier than those who do not have these changes. These changes are found more often in African Americans. Researchers want to study the MC3R in African American adults to see how these changes may affect fat metabolism. They will look at overweight adults with either the most common genetic code for the MC3R or a rare variant.
Objectives:
- To study the role of the MC3R in body weight and fat metabolism.
Eligibility:
- Healthy African American volunteers between 18 and 55 years of age.
- Volunteers must be overweight (body mass index at least 30 kg/m2) but weigh less than 450 lbs.
Design:
- The study consists of an outpatient screening visit and a 7-day inpatient visit with dietary studies.
- Participants will be screened with a physical exam and medical history. Blood samples will be collected. (Participants will need to fast for 10 hours before giving blood samples.) A body scan will be given to determine fat, bone, and muscle content. Participants will complete a 3-day dietary assessment to record their food and drink consumption. They will also have an exercise test to look at heart and lung function.
- Participants will have a 7-day inpatient stay. They will have a regular diet for the first 3 days of the study. For the final 4 days, they will have a diet with a higher fat content.
- During the inpatient visit, participants will have the following study procedures:
- Body measurements
- Daily exercise routine
- Imaging studies of the body
- Measurement of a whole day s energy expenditure (spending one day in metabolic chamber-day 5)
- Frequent blood samples
- Urine collection for 24 hours (days 3 and 7)
- Fat biopsy (collection of a small sample of fat tissue from under the skin on the abdomen)
- Insulin and metabolism tests while eating the two different diets (day 4 and day 7).
- After the final insulin and metabolism test, participants will be discharged from the study.
详细描述
Our prior studies have found that children with homozygosity for two rare Melanocortin 3 Receptor (MC3R) polymorphisms (T6K+V81I) have greater fat mass compared to wild type children. These polymorphisms are about 10-fold more prevalent in Non-Hispanic Black than White Americans. In vitro, T6K+V81I causes MC3R hypofunction. Since mouse models and limited human data suggest the MC3R may be involved in regulating substrate oxidation, and therefore fatty acid disposal, we propose to study 30 Non-Hispanic Black BMI-matched subjects with homozygous T6K+V81I or wild-type MC3R to compare substrate turnover (fatty acids and glucose) during fasting and under conditions of hyperinsulinemia after adaptation from a normal-fat to a high-fat isocaloric diet. Using adipocytes obtained from biopsies, we will also study glucose and fatty acid uptake, storage and mobilization in vitro. We hypothesize that this study will shed light on the role of the MC3R in substrate metabolism and energy expenditure, and will yield information that may assist in the development of more effective approaches for the treatment of obesity in Non-Hispanic Black Americans.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Free fatty acid reflux rate measured on a high- fat diet during the hyperinsulinemic state
时间窗: 3 hours
FFA flux by isotopic study
次要结局
- Free fatty acid flux rate in the post-absorptive state and estimates of whole body glucose disposal and endogenous glucose production assessed during postabsorptive and hyperinsulinemic states on both diets(4 days)