Obesity
Conditions
Brief summary
The investigators are examining the extent gut permeability explains observed inflammation in normal-weight and metabolically healthy obesity (and potentially cardiovascular disease risk).
Detailed description
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.
Interventions
Each participant will provide a blood and fecal sample.
Sponsors
Study design
Eligibility
Inclusion criteria
* Control group: normal BMI, body fat percentage \< 25% for men and \< 35% for women, \< 1 of the following: blood pressure \>130/85 mmHg, fasting glucose \>100 mg/dL, fasting triglycerides \>150 mg/dL, HDL cholesterol \< 40 mg/dL (men) or \< 50 mg/dL (women). * Normal-weight obesity group: normal BMI, body fat percentage \> 25% for men and \> 35% for women. * Metabolically healthy obesity: BMI \> 30, body fat percentage \> 25% for men and \> 35% for women, and \< 1 of the following: blood pressure \>130/85 mmHg, fasting glucose \>100 mg/dL, fasting triglycerides \>150 mg/dL, HDL cholesterol \< 40 mg/dL (men) or \< 50 mg/dL (women). * Metabolic syndrome group: BMI \> 30, body fat percentage \> 25% for men and \> 35% for women, and 2 or more of the following: blood pressure \>130/85 mmHg, fasting glucose \>100 mg/dL, fasting triglycerides \>150 mg/dL, HDL cholesterol \< 40 mg/dL (men) or \< 50 mg/dL (women).
Exclusion criteria
* Presence of pacemaker * Pregnant * Cardiometabolic disease (e.g., diabetes, cardiovascular disease) * Disease that is inflammatory in nature (e.g., inflammatory bowel disease, rheumatoid arthritis) * Postmenopausal status * Use of tobacco products * Using illicit drugs * Using lipid lowering drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Indicators of gut permeability | 1 year | 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). |
| C-reactive protein | 1 year | The investigators will measure the marker of chronic inflammation C-reactive protein (CRP) using an ELISA. |
| Inflammatory cytokines | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal microbiota | 1 year | The investigators will assess microbiota composition in a subset of individuals (\ n=10 per group). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Body composition assessment with dual-energy X-ray absorptiometry (DXA) | Through study completion, an average of 1 year | 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). |
| Lipid panel with Abbott Piccolo Xpress Clinical Chemistry Analyzer | Through study completion, an average of 1 year | The investigators will perform a lipid panel on all participants. |
Countries
United States