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The investigators are examining the extent gut permeability explains observed inflammation in normal-weight and metabolically healthy obesity (and potentially cardiovascular disease risk).
Cardiovascular disease (CVD) is responsible for 25% of deaths in the United States, and chronic inflammation contributes to risk. A growing body of evidence suggests that gut-derived bacterial components (e.g., lipopolysaccharide or LPS) entering the bloodstream when the gut barrier fails (i.e., intestinal permeability) are a prominent source of inflammation in cardiometabolic conditions such as metabolic syndrome, coronary artery disease, and type 2 diabetes. Two groups that are at > 2x the risk for CVD, but largely still free of overt disease, are those with metabolically healthy obesity and normal-weight obesity. Those with metabolically healthy obesity - defined as having an obese body mass index (BMI) but other clinical risk factors in the normal range (e.g., blood lipids) - and normal-weight obesity - defined as having a normal BMI yet high percent body fat - generally display little evidence of clinical risk, but present with elevated inflammatory markers including C-reactive protein (CRP), tumor necrosis factor (TNF)-a, and interleukin (IL)-6). Therefore, it is likely that chronic inflammation is largely driving CVD risk in metabolically healthy and normal-weight obesity, but the source of this inflammation remains unclear. The primary aim of the proposed project is to determine the extent that markers of intestinal permeability are elevated in metabolically healthy obesity and normal-weight obesity compared to healthy controls and individuals with metabolic syndrome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | The control group for this study will consist of individuals with normal BMI (18.5 - 24.9 kg/m2), body fat percent < 25% (male) or < 35% (female), and up to 1 other risk factor among the following: blood pressure > 130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, and HDL < 40 (male) or < 50 (female). |
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| Normal-weight obesity | Individuals with normal-weight obesity will be defined as having normal BMI (18.5 - 24.9 kg/m2), body fat percent > 25% (male) or > 35% (female). |
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| Metabolically Healthy Obesity | Metabolically healthy obesity will be defined as having an obese BMI (> 30 kg/m2), body fat percent < 25% (male) or < 35% (female), and up to 1 other risk factor among the following: blood pressure > 130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, and HDL < 40 (male) or < 50 (female). |
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| Metabolic Syndrome | Metabolic syndrome will be defined using the international Diabetes Federation criteria of an obese BMI ( > 30 kg/m2) and 2 or more of the following risk factors: blood pressure > 130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, and HDL < 40 (male) or < 50 (female). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples. | Other | Each participant will provide a blood and fecal sample. |
| Measure | Description | Time Frame |
|---|---|---|
| Indicators of gut permeability | The investigators will measure serum markers of gut permeability as primary outcomes (i.e., lipopolysaccharide binding protein, soluble cluster of differentiation (CD)14, intestinal fatty acid binding protein). | 1 year |
| C-reactive protein | The investigators will measure the marker of chronic inflammation C-reactive protein (CRP) using an ELISA. | 1 year |
| Inflammatory cytokines | The investigators will measure a panel of serum inflammatory cytokines that includes granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, and tumor necrosis factor (TNF)-α using a bioplex assay. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Fecal microbiota | The investigators will assess microbiota composition in a subset of individuals (~n=10 per group). | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Body composition assessment with dual-energy X-ray absorptiometry (DXA) | The investigators will perform DXA scans on all participants to assess body composition parameters (i.e., body fat percent, lean mass, percent, visceral adipose tissue). | Through study completion, an average of 1 year |
| Lipid panel with Abbott Piccolo Xpress Clinical Chemistry Analyzer |
Inclusion Criteria:
Exclusion Criteria:
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The study populations of interest are those with normal weight obesity (normal BMI and high body fat percent) and metabolically healthy obesity (obese BMI, but largely normal cardiovascular risk factors).
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 208 Nancy Randolph Davis, Oklahoma State University | Recruiting | Stillwater | Oklahoma | 74078 | United States |
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The investigators are collecting serum and fecal samples.
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The investigators will perform a lipid panel on all participants. |
| Through study completion, an average of 1 year |
| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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