Beige Fat, Energy, and the Natriuretic Peptide System

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Recruiting

CT.gov ID

NCT04357964

Collaborator

Vanderbilt University Medical Center (Other)

100

Enrollment

Locations

38.5

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 13, 2020

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
obese and lean individuals obese and lean individuals

Outcome Measures

Primary Outcome Measures

adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by obesity status [Study Day 1]
Primary endpoint is adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by obesity status.

Secondary Outcome Measures

Associations of adipose tissue gene expression of UCP1 with natriuretic peptide markers [Study Day 1]
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)
adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by race [Study Day 1]
The investigators will determine adipose tissue gene expression of UCP1 (Uncoupling Protein 1), and analyze differences by race (blacks compared with whites).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Valley Healthcare System Nashville Campus, Nashville, TN	Nashville	Tennessee	United States	37212-2637
2	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232