Metaflammatory responses during obesity: Pathomechanism and treatment

Obesity induced inflammation acts as a reflex produced due to altered metabolic homeostasis in accordance to the nutrient overload on the metabolic cells. It involves up-regulation of the genes encoding for cytokines, chemokines and other inflammatory mediators through activated transcription factors - nuclear factor-kB, activator protein-1, nuclear factor of activated T cells and signal transducer and activator of transcription 3. These execute macromolecular innate immune cell sensor - inflammasome to activate caspase-1 pathway resulting in proteolytic maturation. Secretion of pro-inflammatory cytokines including TNF-alpha, IL-6, CRP, IL-1 beta, etc. from the M1 macrophages of white adipose tissue is increased, whereas there occurs a steep decline in the production of anti-inflammatory cytokines like IL-10, IL-Ra, adiponectin. Not only the adipose tissue, but also the immune cells, liver, brain, muscles and pancreas suffers from the inflammatory insult during obese condition and are exaggeratedly affected. The inflammatory kinases like JNK and IKK apart from inhibiting insulin action and glucose uptake, down-regulate transcriptional process resulting in increased expression of pro-inflammatory cytokines. Macrophage-like Kupffer cells initiate the inflammatory process in the liver preceding the inflammatory signals produced by the white adipose tissue which may further lead to hepatic-necro-inflammation. The muscle-fibre is affected by the cytokines and therefore results in decreased glycogen synthesis. The triggered hypothalamic-pituitary-adrenal axis further affects the expression of inflammatory cytokines thus altering insulin homeostasis and initiating glucose intolerance. Antiinflammatory treatment so as to curb the severity of inflammatory responses includes administration of synthetic drugs to target the actual inflammatory molecules and various therapeutic interventions. (C) 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.