Beige Fat, Energy, and the Natriuretic Peptide System

Study Overview
=================
Brief Summary
-----------------
Obese individuals experience an increased risk of cardiovascular and metabolic diseases. Evidence from genetic studies indicate that the natriuretic peptide (NP) system may protect against these diseases. NP levels differ by obesity status and race has not been established in humans. Thus, the investigators propose a study in which will quantify adipose tissue gene expression and energy expenditure in states of NP deficiency in humans. The overarching postulate is that obese and black individuals have NP deficiencies that contribute to less beige adipose tissue and lower energy expenditure.

Detailed Description
-----------------
Obesity represents a serious public health burden. Obese individuals experience increased risk of cardiovascular and metabolic cardiometabolic disease, including insulin diabetes, resistance, hypertension, and dyslipidemia. Obesity and obesity-associated cardiometabolic dysfunction are significant contributors to morbidity and mortality in Veterans. This indicates that obesity and cardiometabolic dysfunction are complex and multifactorial, and suggests that there are additional factors that contribute to the pathogenesis of obesity and its associated cardiometabolic risk that have been discovered. Moreover, some of the pharmacologic therapies for obesity can have adverse cardiovascular effects. Thus, it is crucial to improve the understanding of the multiple pathways contributing to the pathogenesis of obesity and obesity-associated cardiometabolic risk, including the identification of novel relevant pathways, in order to develop more effective treatments for these diseases. The proposed work will form a foundation for future high-impact studies of mechanisms for adiposity and cardiometabolic disease.

Official Title
-----------------
Beige Fat, Energy, and the Natriuretic Peptide System (ENDA-025-17S)

Conditions
-----------------
Obesity

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women ages 18-55 years Body Mass Index (BMI) >= 18.5 and <25 kg/m2 (lean), or BMI 30 kg/m2 (obese) Exclusion Criteria: Significant pulmonary, liver, or renal disease Heart failure (any type) or unstable coronary artery disease Diabetes Mellitus (Types 1 and 2) Thyroid dysfunction Active malignancy Chronic inflammatory diseases, such as inflammatory bowel disease, hepatitis, rheumatoid arthritis Current use of medications likely to affect energy homeostasis, including glucocorticoids, amphetamines, and beta blockers Currently pregnant or breastfeeding, or unwilling to avoid becoming pregnant or breastfeeding during study duration Significant claustrophobia that would prevent the use of the metabolic cart as part of the study protocol Hemoglobin A1c (HbA1c) >= 6.5% Liver Function Tests (LFTs) elevated >3x upper limit of normal Estimated Glomerular Filtration Rate (eGFR) <40 ml/min Currently abnormal thyroid stimulating hormone (TSH)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| obese and lean individuals<br>obese and lean individuals | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by obesity status | Primary endpoint is adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by obesity status. | Study Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Associations of adipose tissue gene expression of UCP1 with natriuretic peptide markers | The investigators will determine associations of adipose tissue gene expression of UCP1 with natriuretic peptide markers (natriuretic peptide receptor gene expression in adipose tissue, and circulating natriuretic peptide levels) | Study Day 1 | 
| adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by race | The investigators will determine adipose tissue gene expression of UCP1 (Uncoupling Protein 1), and analyze differences by race (blacks compared with whites). | Study Day 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, adipose tissue, beige adipose tissue, cardiovascular physiology, B-type natriuretic peptide, metabolism