Beige Fat, Energy, and the Natriuretic Peptide System

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

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)

Primary Outcome Measures

Name	Time	Method
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 (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 Outcome Measures

Name	Time	Method
Associations of Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1) 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).

Locations (2): VA TVHS Nashville
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Nashville, Tennessee, United States
Vanderbilt University Medical Center
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Nashville, Tennessee, United States