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

Abstract

Susanne Kristine Aune,1,2 Ragnhild Helseth,1,3 Are A Kalstad,1 Kristian Laake,1 Sissel Åkra,1 Harald Arnesen,1,2 Svein Solheim,1,3 Ingebjørg Seljeflot1– 3 1Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; 2Faculty of Medicine, University of Oslo, Oslo, Norway; 3Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayCorrespondence: Susanne Kristine Aune, Center for Clinical Heart Research, Oslo University Hospital (OUH) Ullevål, Pb 4956 Nydalen, Oslo, 0424, Norway, Tel [phone], Email [email protected]; [email protected]: 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.Keywords: endotoxemia, lipopolysaccharide, LPS-binding protein, gut leakage, obesity, metabolic syndrome, coronary artery disease

Keywords

• endotoxemia. lipopolysaccharide. lps-binding protein. gut leakage. obesity. metabolic syndrome. coronary artery disease