Infection-induced inflammatory response of adipocytes in vitro

Abstract

Background: Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes. In this study we investigated whether adipocytes can be infected and whether this results in production of inflammatory cytokines relevant for the development of atherosclerosis and diabetes. Methods: Pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36, influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) were measured in supernatants. Results: Infection of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from 192 ± 22 pg ml À1 (uninfected) to 1030 ± 86 pg ml À1 , 838 ± 59 pg ml À1 and 1241 ± 191 pg ml À1 , respectively (all Po0.01 vs control). In addition, Ad-36 infection slightly reduced PAI production in adipocytes (285 ± 26.8 ng ml À1 vs uninfected: 477 ± 71.2 ng ml À1 ; P ¼ 0.05) and pre-adipocytes (709±43.3 ng ml À1 vs uninfected: 1071±71.8 ng ml À1 ; Po0.01). In contrast, human Ad type 2 did not exert any effect on IL-6 or PAI production. None of the microorganisms induced significant changes in adiponectin and/or TNF-a production. Conclusions: Adipocytes can be infected with several microorganisms in vitro. Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of IL-6 which might contribute to chronic low-grade inflammation, a process known to be involved in the development of cardiovascular diseases and type 2 diabetes.

Human obesity relationship with Ad36 adenovirus and insulin resistance

“…27 Among the investigated mechanisms, Ad36 infection reduces the secretion of leptin and induces greater lipid accumulation in preadipocytes; 28 moreover, infection of adipocytes with Ad-36 leads to increased production of IL-6, which might contribute to chronic lowgrade inflammation, with a process known to be involved in the development of cardiovascular diseases and type 2 diabetes. 29 The increased prevalence of essential hypertension observed in our study could be conjecturally explained also by the production of inflammatory cytokines, induced by Ad36 infection, relevant for the development of atherosclerosis and diabetes. Obesity is significantly more prevalent in women with earlier Ad36 infection.…”

How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?

“…CMV mainly infects fibroblasts; epithelial, endothelial, and stromal cells; smooth muscle cells (Haspot et al 2012); and adipocytes (Bouwman et al 2008), which are believed to present CMVantigens in the context of MHC class I. The inflammatory response initiated by CMV-stimulated cells elicits the release of pro-inflammatory cytokines secreted from cells of the immune system and generates a vicious cycle, leading to immune system remodeling.…”

The association of body mass index, waist and hip circumference, and waist–hip ratio with Chlamydia pneumoniae IgG antibodies and high-sensitive C-reactive protein at 31 years of age in Northern Finland Birth Cohort 1966

“…Our results are supported by recent findings showing that C. pneumoniae is capable of infecting murine pre-adipocytes and adipocytes, 20 and human adipocytes derived from subcutaneous pre-adipocytes. 19 Furthermore, in LDLR À/À mice repeatedly infected with C. pneumoniae, the pathogen was found in preadipocytes in the adipose tissue, 20 demonstrating that C. pneumoniae is capable of disseminating into fat tissue, also in vivo, possibly through infected monocytes/macrophages. 18 C. pneumoniae infection in adipocytes might also be able to induce accumulation of fat, as Chlamydial infections have been shown to influence accumulation and/or trafficking of lipids in host cells in vitro, [40][41][42] and to induce liver steatosis in ApoE-deficient mice.…”

“…17,18 The possible route of C. pneumoniae from lungs to other tissues could be through bronchoalveolar macrophages, 18 and recent reports suggest that C. pneumoniae is also capable of infecting both murine and human preadipocytes and adipocytes. 19,20 Slightly elevated levels of serum C-reactive protein (CRP) are considered as a marker of systemic low-grade inflammation associated with obesity, insulin resistance and metabolic syndrome, 21 and future cardiovascular events. [21][22][23][24][25][26] Previous studies concerning the association between C. pneumoniae infection markers and overweight/obesity have focused only on BMI and/or have had rather small sample size, [5][6][7][8]10,12,[27][28][29][30][31][32] the results being contradictory.…”