Obesity
Conditions
Keywords
adipose tissue, beige adipose tissue, cardiovascular physiology, B-type natriuretic peptide, metabolism, obesity
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.
Interventions
None listed
Sponsors
Vanderbilt University Medical Center
VA Office of Research and Development
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Pre-assignment details
Enrolled subjects underwent a screening visit to determine eligibility for the study. The screening visit included a medical history, physical examination, calculation of BMI, and a blood draw for CMP, CBC, HbA1c, TSH, and free T4. A pregnancy test was completed on female subjects of child-bearing potential. Eligible subjects who still wished to participate in the study were then enrolled for the main study visit.
Participants by arm
| Arm | Count |
|---|---|
| Lean Individuals lean individuals (BMI \>= 18.5 and \<25 kg/m2) | 37 |
| Obese Individuals obese individuals (BMI\>= 30 kg/m2) | 81 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adipose sample was insufficient quality | 0 | 1 |
| Overall Study | Deemed not to have enough sufficient adipose tissue to undergo subcutaneous adipose biopsy | 5 | 0 |
| Overall Study | Did not have usable primary endpoint data due to insufficient or low-quality adipose sample | 13 | 0 |
Baseline characteristics
| Characteristic | Lean Individuals | Total | Obese Individuals |
|---|---|---|---|
| Age, Continuous | 39 years | 47 years | 52 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 19 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 31 Participants | 95 Participants | 64 Participants |
| Region of Enrollment United States | 37 Participants | 118 Participants | 81 Participants |
| Sex: Female, Male Female | 11 Participants | 61 Participants | 50 Participants |
| Sex: Female, Male Male | 26 Participants | 57 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 55 | 0 / 22 |
| other Total, other adverse events | 8 / 55 | 0 / 22 |
| serious Total, serious adverse events | 0 / 55 | 0 / 22 |
Outcome results
Primary
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.
Time frame: Study Day 1
Population: All participants who had data for primary endpoint (adipose tissue UCP1 gene expression).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean Individuals | Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status | 7.79 fold change |
| Obese Individuals | Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status | 24.33 fold change |
p-value: <0.01Kruskal-Wallis
Secondary
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).
Time frame: Study Day 1
Population: All participants who had data for primary endpoint (adipose tissue UCP1 gene expression), and who also self-reported their race as white or black.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean Individuals | Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Race | 14.7 fold change |
| Obese Individuals | Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Race | 20.9 fold change |
p-value: 0.52Kruskal-Wallis
Secondary
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)
Time frame: Study Day 1
Population: Correlation between UCP1 gene expression and natriuretic peptide receptor-C (NPR-C) gene expression. The groups are combined in this analysis because the investigators had pre-specified that this secondary outcome would analyze this correlation across all individuals (lean and obese combined) for whom gene expression data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lean Individuals | Associations of Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1) With Natriuretic Peptide Markers | 0.28 correlation coefficient |
p-value: <0.01Pearson correlation