Beige Fat, Energy, and the Natriuretic Peptide System

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

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 137

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37212
      • VA TVHS Nashville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Healthy volunteers who are U.S. veterans

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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 (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.	Study Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Associations of Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1) 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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Alp Ikizler, MD, Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2020
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: obesity; metabolism; adipose tissue; B-type natriuretic peptide; beige adipose tissue; cardiovascular physiology
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: ENDA-025-17S-1; 1IK2CX001678 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No