Gut Permeability-related Inflammation and Cardiovascular Disease Risk in Normal-weight and Metabolically Healthy Obesity

Gut Permeability-related Inflammation and Cardiovascular Disease Risk in Normal-weight and Metabolically Healthy Obesity

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.

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