Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review).

Abstract

Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co‑morbidities, including type‑2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non‑alcoholic fatty liver disease, kidney diseases, respiratory disorders, sleep apnea, musculoskeletal disorders and osteoarthritis, subfertility, psychosocial problems and certain types of cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro‑inflammatory polarization of macrophages toward the M1 phenotype, in adipose tissue (AT), with subsequent increased production of pro‑inflammatory cytokines and adipokines, inducing therefore an overall, systemic, low‑grade inflammation, which contributes to metabolic syndrome (MetS), insulin resistance (IR) and T2DM. Targeting inflammatory mediators could be alternative therapies to treat obesity, but their safety and efficacy remains to be studied further and confirmed in future clinical trials. The present review highlights the molecular and pathophysiological mechanisms by which the chronic low‑grade inflammation in AT and the production of reactive oxygen species lead to MetS, IR and T2DM. In addition, focus is given on the role of anti‑inflammatory agents, in the resolution of chronic inflammation, through the blockade of chemotactic factors, such as monocytes chemotractant protein‑1, and/or the blockade of pro‑inflammatory mediators, such as IL‑1β, TNF‑α, visfatin, and plasminogen activator inhibitor‑1, and/or the increased synthesis of adipokines, such as adiponectin and apelin, in obesity‑associated metabolic dysfunction.