Links Between Adipose Tissue Gene Expression of Gut Leakage Markers, Circulating Levels, Anthropometrics, and Diet in Patients with Coronary Artery Disease.

ABSTRACT

Background: Recent studies suggest gut-derived lipopolysaccharide (LPS)-translocation to play a role in both systemic inflammation and in inflammatory adipose tissue. We aimed to investigate whether circulating LPS-related inflammatory markers and corresponding genetic expression in adipose tissue were associated with obesity, cardiometabolic risk factors, and dietary habits in patients with coronary artery disease. Methods: Patients (n=382) suffering a myocardial infarction 2-8 weeks prior to inclusion were enrolled in this cross-sectional study. Subcutaneous adipose tissue (SAT), taken from the gluteal region, and fasting blood samples were collected at inclusion for determination of genetic expression of LPS-binding protein (LBP), CD14, toll-like receptor 2 (TLR2), and TLR4 in SAT, and LPS, LBP, and soluble cluster of differentiation 14 (sCD14) in the circulation. All patients filled out a dietary registration form. Results: Patients (median age 74 years, 25% women), had a median body mass index (BMI) of 25.9 kg/m2. Circulating levels of LBP correlated to BMI (p=0.02), were significantly higher in overweight or obese (BMI≥25 kg/m2) compared to normal- or underweight patients (BMI<25 kg/m2), and were significantly elevated in patients with T2DM, hypertension, and MetS, compared to patients without (p≤0.04, all). In SAT, gene expression of CD14 and LBP correlated significantly to BMI (p≤0.001, both), and CD14 and TLR2 expressions were significantly higher in patients with T2DM and MetS compared to patients without (p≤0.001, both). Circulating and genetically expressed CD14 associated with use of n-3 PUFAs (p=0.008 and p=0.003, respectively). No other significant associations were found between the measured markers and dietary habits. Conclusion: In patients with established CAD, circulating levels of LBP and gene expression of CD14 and TLR2 in SAT were related to obesity, MetS, T2DM, and hypertension. This suggests that the LPS-LBP-CD14 inflammatory axis is activated in the chronic low-grade inflammation associated with cardiometabolic abnormalities, whereas no significant associations with dietary habits were observed.