Obesity
Conditions
Brief summary
The objective of this study is to better define the role of the hormone angiotensin-(1-7) in energy balance. We will test the overall hypothesis that angiotensin-(1-7) increases resting energy expenditure and promotes markers of heat production (thermogenesis) in white adipose tissue in human obesity.
Detailed description
Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to produce positive cardiovascular and metabolic effects in animal models. In this study, the investigators will determine if angiotensin-(1-7) can increase resting energy expenditure and promote white adipose tissue heat production (thermogenesis) in obese human subjects. The investigators will perform a randomized, double-blind, two-arm parallel group study to determine effects of acute intravenous angiotensin-(1-7) versus saline infusion on resting energy expenditure measured by indirect calorimetry in obese human participants. In addition, blood pressure and heart rate will be measured and blood samples obtained to measure for changes in circulating renin-angiotensin system and metabolic hormones. Abdominal subcutaneous white adipose biopsies will also be obtained from obese human participants during acute angiotensin-(1-7) versus saline infusions to examine for changes in gene expression for markers of thermogenesis. The findings from these studies will advance understanding of hormonal mechanisms involved in the etiology of obesity, and provide new insight into the potential for targeting angiotensin-(1-7) to improve energy balance in human obesity.
Interventions
DRUGSaline
Saline will be used as the placebo comparator.
This is a biologically active beneficial hormone of the renin-angiotensin system.
Sponsors
Amy Arnold
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Men and women of all races * Capable of giving informed consent * Age 18-60 years * Body mass index (BMI) between 30-40 kg/m2 * Satisfactory history and physical exam
Exclusion criteria
* Age ≤ 17 or ≥ 61 years * Pregnant, nursing, or postmenopausal women * Decisional impairment * Prisoners * Alcohol or drug abuse * Current smokers * Highly trained athletes * Claustrophobia * Subjects with \>5% weight change in the past 3 months * Evidence of type I or type II diabetes (fasting glucose \> 126 mg/dL or use of anti-diabetic medications) * History of serious cardiovascular disease other than hypertension (e.g. myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke, transient Ischemic attack). * History or presence of immunological or hematological disorders * Impaired hepatic function (aspartate aminotransferase or alanine aminotransferase levels \>2 times upper limit of normal range) * Impaired renal function (serum creatinine \>2.0 mg/dl) * Anemia * Treatment with anticoagulants (e.g. warfarin) * Treatment with chronic systemic glucocorticoid therapy (\>7 consecutive days in 1 month) * Treatment with medications influencing energy expenditure (e.g. psychostimulants) * Treatment with any investigational drug in the 1-month preceding the study * Inability to give, or withdraw, informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting energy expenditure | 120 minutes | Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion. |
| Uncoupling protein 1 | 120 minutes | White adipose tissue biopsies will be taken at end of angiotensin-(1-7) versus saline infusion to assess gene expression of the heat producing (thermogenic) marker uncoupling protein 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | 120 minutes | Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion |
| Heart rate | 120 minutes | Change in heart rate following angiotensin-(1-7) versus saline infusion |
Other
| Measure | Time frame | Description |
|---|---|---|
| Insulin | 120 minutes | Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion |
| Glucose | 120 minutes | Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion |
| Fatty acids | 120 minutes | Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion |
| Skin temperature | 120 minutes | Change in skin temperature following angiotensin-(1-7) versus saline infusion |
| Angiotensin-(1-7) | 120 minutes | Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion |
| Renin | 120 minutes | Change in plasma renin activity following angiotensin-(1-7) versus saline infusion |
| Aldosterone | 120 minutes | Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion |
| Angiotensin II | 120 minutes | Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion |
| Skin blood flow | 120 minutes | Change in skin blood flow following angiotensin-(1-7) versus saline infusion |
| Abdominal heat production | 120 minutes | Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion |
| Catecholamines | 120 minutes | Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion |
Countries
United States
Outcome results
None listed