👤 Igor Shaposhnik

Visceral obesity plays a pivotal role in initiating and sustaining chronic systemic inflammation through complex interactions involving adipose tissue dysfunction, insulin resistance, immune system activation, and gut microbiome composition. Visceral obesity is also hypothesized to contribute to the development and progression of extraintestinal manifestations and complications in inflammatory bowel disease (IBD). The aim was to evaluate the interrelationships between ultrasound-measured visceral and subcutaneous adipose tissue thickness with carotid artery atherosclerosis indicators in IBD patients. The study included 90 patients with IBD aged 40-64 years. All patients underwent duplex ultrasound scanning of the carotid arteries with measurement of carotid plaque burden indicators. Ultrasound measurements of subcutaneous and visceral adipose tissue thickness (ATT) were performed: minimal subcutaneous adipose tissue thickness (mSATT), maximal preperitoneal adipose tissue thickness (mPATT), periumbilical subcutaneous adipose tissue thickness (PSATT), visceral abdominal adipose tissue thickness, peri- and pararenal adipose tissue thickness. Ultrasound-derived indicators of visceral obesity (mPATT and abdominal ATT), but not BMI or WC, were associated with an increased odds ratio for the presence of carotid plaque after adjustment for sex and age. Both mPATT and abdominal ATT demonstrated positive correlations with apoB concentration, LDL-C, sdLDL, eLDL-TG, and inverse correlations with adiponectin concentration. In patients with IBD aged 40-64 years, visceral adipose tissue thickness measured by ultrasound and WC were associated with the carotid plaque burdens. Ultrasound-measured mPATT and abdominal ATT, but not BMI and WC, were independently associated with carotid atherosclerosis in patients with IBD. Show less

Experimental and clinical studies link Chlamydia pneumoniae infection to atherogenesis and atherothrombotic events, but the underlying mechanisms are unclear. We tested the hypothesis that C. pneumoniae-induced acceleration of atherosclerosis in apolipoprotein E (ApoE)(-/-) mice is reciprocally modulated by activation of TLR-mediated innate immune and liver X receptor alpha (LXRalpha) signaling pathways. We infected ApoE(-/-) mice and ApoE(-/-) mice that also lacked TLR2, TLR4, MyD88, or LXRalpha intranasally with C. pneumoniae followed by feeding of a high fat diet for 4 mo. Mock-infected littermates served as controls. Atherosclerosis was assessed in aortic sinuses and in en face preparation of whole aorta. The numbers of activated dendritic cells (DCs) within plaques and the serum levels of cholesterol and proinflammatory cytokines were also measured. C. pneumoniae infection markedly accelerated atherosclerosis in ApoE-deficient mice that was associated with increased numbers of activated DCs in aortic sinus plaques and higher circulating levels of MCP-1, IL-12p40, IL-6, and TNF-alpha. In contrast, C. pneumoniae infection had only a minimal effect on atherosclerosis, accumulation of activated DCs in the sinus plaques, or circulating cytokine increases in ApoE(-/-) mice that were also deficient in TLR2, TLR4, or MyD88. However, C. pneumoniae-induced acceleration of atherosclerosis in ApoE(-/-) mice was further enhanced in ApoE(-/-)LXRalpha(-/-) double knockout mice and was accompanied by higher serum levels of IL-6 and TNF-alpha. We conclude that C. pneumoniae infection accelerates atherosclerosis in hypercholesterolemic mice predominantly through a TLR/MyD88-dependent mechanism and that LXRalpha appears to reciprocally modulate and reduce the proatherogenic effects of C. pneumoniae infection. Show less