Metabolic Inflammation and Insulin Resistance in Obesity

Abstract

Obesity is becoming an epidemic in the United States and worldwide and increases risk for many diseases, particularly insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The mechanisms linking obesity with these diseases remain incompletely understood. Over the past 2 to 3 decades, it has been recognized that in obesity, inflammation, with increased accumulation and inflammatory polarization of immune cells, takes place in various tissues, including adipose tissue, skeletal muscle, liver, gut, pancreatic islet, and brain and may contribute to obesity-linked metabolic dysfunctions, leading to insulin resistance and type 2 diabetes mellitus. Therapies targeting inflammation have shed light on certain obesity-linked diseases, including type 2 diabetes mellitus and atherosclerotic cardiovascular disease, but remain to be tested further and confirmed in clinical trials. This review focuses on inflammation in adipose tissue and its potential role in insulin resistance associated with obesity.

COVID-19 and obesity in childhood and adolescence: a clinical review

“…However, some patients trigger an uncontrolled process, known as a cytokine storm, which causes tissue damage and intense homeostatic dysregulation, leading to damage of several organic functions, especially regarding the respiratory area.79 Obese patients are known to have chronic subclinical inflammation, characterized by a permanent inflammatory state, albeit of mild intensity. 80 High serum concentrations of C-reactive protein and IL-6 prove this process 61 which can start early. It is believed that, at least in part, this process is due to cytokines, particularly adipokines with inflammatory properties, produced by adipose tissue 61 and also the drop in adiponectin, which has anti-inflammatory properties.…”

Роль Основных Эффекторных Клеток Врожденной Иммунной Системы В Развитии Метавоспаления Жировой Ткани При Ожирении

“…Відповідно до сучасної концепції, ожиріння розглядається як захворювання, що перебігає з розвитком хронічної запальної реакції з низьким рівнем активності, що отримала назву метазапалення [1,2,47,91]. Запальна реакція при ожирінні спочатку виникає в ре-зультаті надмірного накопичення жиру в адипоцитах і зміни спектра продукованих ними продуктів: зниження рівня секреції адипонектину, IL-10, TGF-β; посилення синтезу резистину, лептину, CCL2, IL-6, TNF-α.…”

Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes

“…These mechanisms are commonly considered the link between chronic caloric excess and AT meta-inflammation. Some of these mechanisms include dysregulation of fatty acid homeostasis, increased adipocyte size and death, local hypoxia, mitochondrial dysfunction, increased reactive oxygen species production, endoplasmic reticulum, and mechanical stress leading to extracellular matrix remodeling and fibrosis [ 5 , 6 ]. These triggers converge on the activation of the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-kB) pathways, commonly considered signaling hubs.…”

“…The activation of these pathways increases the production of pro-inflammatory cytokines and promotes the recruitment of a variety of immune cells, including macrophages, T cells, B cells, neutrophils, and others. These immune cells produce a large number of type 1 inflammatory molecules and also interact directly with each other to induce a type 1 inflammatory environment in AT resulting in local (AT) and systemic insulin resistance and T2D [ 5 , 6 ]. Therefore, inflamed AT is characterized by the combination of an increase in total macrophages and an increased ratio of «classically-activated» proinflammatory M1 phenotype versus «alternatively-activated» anti-inflammatory M2 phenotype macrophages [ 4 , 73 ] that is typical of lean individuals [ 74 ].…”

“…The long-term excessive AT mass, progressively leads to the appearance of a marked inflammatory profile and to its secondary dysfunction (i.e., impaired expandability and plasticity) [ 4 ]. The inability of further AT expansion accelerates fat spillover from AT to skeletal muscle and liver, resulting in ectopic fat deposition and insulin resistance in these tissues, which play vital roles in systemic insulin resistance and T2D [ 5 , 6 ]. These modifications that strongly contribute to T2D and obesity comorbidity development [ 7 , 8 ], makes AT a putative new therapeutic target.…”