Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications

Abstract

Obesity is characterized by the excessive deposition of fat that may interfere with the normal metabolic process of the body. It is a chronic condition associated with various metabolic syndromes, whose prevalence is grossly increasing, and affects both children and adults. Accumulation of excessive macronutrients on the adipose tissues promotes the secretion and release of inflammatory mediators, including interleukin-6 (IL-6), interleukin 1β, tumor necrotic factor-α (TNF-α), leptin, and stimulation of monocyte chemoattractant protein-1 (MCP-1), which subsequently reduce the production of adiponectin thereby initiating a proinflammatory state. During obesity, adipose tissue synthesizes and releases a large number of hormones and cytokines that alter the metabolic processes, with a profound influence on endothelial dysfunction, a situation associated with the formation of atherosclerotic plaque. Endothelial cells respond to inflammation and stimulation of MCP-1, which is described as the activation of adhesion molecules leading to proliferation and transmigration of leukocytes, which facilitates their increase in atherogenic and thromboembolic potentials. Endothelial dysfunction forms the cornerstone of this discussion, as it has been considered as the initiator in the progression of cardiovascular diseases in obesity. Overexpression of proinflammatory cytokines with subsequent reduction of anti-inflammatory markers in obesity, is considered to be the link between obesity-induced inflammation and endothelial dysfunction. Inhibition of inflammatory mechanisms and management and control of obesity can assist in reducing the risks associated with cardiovascular complications.

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

“…This process is likely connected to a gradual loss of functional ASCs, a type of MSCs, in AT by reducing their differentiation, motility and immunomodulation capacity as well as impairing their ciliogenesis and pro-angiogenic ability [66]. Inflammation and its associated inflammatory cytokines, including IL-6, TNF-α, IL-1β, and inflammatory factors like C-reactive protein (CRP), are all known to induce endothelial dysfunction in AT [67]. Moreover, the deregulated expression of adipokines like leptin and resistin in AT of obese patients causes increased expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), both leading to vascular dysfunction and oxidative stress [68].…”

Inflammatory and endothelial dysfunction indices among Egyptian females with obesity classes I–III

“…Obesity is known as a perpetual state of chronic low-grade inflammation, through systemic and paracrine increase in levels of cytokines and chemokines [14,15]. In the current study, the serum levels of TNF-α, CRP, IL-6, IL-12, sVCAM-1 and sICAM-1 were evaluated with the progression of obesity classes I-III.…”

“…Definitive work has shown a direct association between the increase in obesity class and the presence of obesity-related comorbidities with the elevated levels of inflammatory biomarkers [17]. The overexpression of proinflammatory cytokines is considered to be the link between obesity-induced inflammation and endothelial dysfunction [15]. In this sense, TNF-α has received considerable attention as one of the key mediators of inflammation involved in obesity and is found in high concentrations in subjects with obesity than in lean [7,18,19].…”

“…Unlike TNF-α, IL-6 principally secreted in an endocrine (systemic) fashion [29] and the expanding AT in obesity may contribute high levels of IL-6 in the circulation [20,28]. Consequently, the accumulation of excessive macronutrients in the ATs in obesity, stimulates the release of inflammatory mediators like TNF-α and IL-6, causing the predisposition of the endothelium toward a proinflammatory state gearing to endothelial dysfunction [15]. Although the levels of IL-6 have been clearly demonstrated to be increased in relation to obesity, we reported that class II obesity group did not have a statistically significant change in levels of that cytokine.…”

“…In this regard, the inflammatory mediators are activated by nuclear factor κB (NF-κB) signaling and regulates the expansion of endothelial cells via increasing the expression of ICAM-1, resulting in the relocation of leukocytes and inducing the progression of atherosclerosis [47]. Also, ICAM-1, VCAM-1 and E-selectin intervene with inflammatory cytokines of the vascular wall to promote extravasations and subsequent endothelial dysfunction [15]. VCAM-1 has a unique pattern of regulation.…”