Beige Fat, Energy, and the Natriuretic Peptide System (ENDA-025-17S)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obesity
- Sponsor
- VA Office of Research and Development
- Enrollment
- 137
- Locations
- 2
- Primary Endpoint
- Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status
- Status
- Completed
- Last Updated
- last year
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.
Investigators
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%
Outcomes
Primary Outcomes
Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status
Time Frame: Study Day 1
Primary endpoint is adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by obesity status (obese vs. lean). Units for primary endpoint are relative UCP1 gene expression (quantified using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR)), normalized to a housekeeping gene.
Secondary Outcomes
- Associations of Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1) With Natriuretic Peptide Markers(Study Day 1)
- Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Race(Study Day 1)