Revista de biología de citocinas

Abstracto

Obesity Induced Metaflammation: Pathophysiology and Mitigation

Monalisa Debnath and Sutripta Sarkar

Obesity is dramatically increasing worldwide and there exists a significant association of its prevalence with Type 2 Diabetes Mellitus, hypertension, cardiovascular diseases etc. The altered homeostasis of nutritionally overloaded metabolic cells marks the development of obesity induced inflammation. It is marked by elevated expression of the genes encoding for cytokines, chemokines and other inflammatory mediators through activated transcription factorsnuclear factor-kB, activator protein-1, nuclear factor of activated T cells and signal transducer and activator of transcription 3 and; execution of a macromolecular innate immune cell sensor- inflammasome to activate caspase-1 pathway resulting in photolytic maturation. In brief, there occurs an evidential increase in pro-inflammatory cytokines released from the M1 macrophages of white adipose tissue including TNF-α, IL-6, CRP, IL-1β, etc. on contrary an observable decrease in anti-inflammatory cytokines like IL-10, IL-Ra, adiponectin etc. released from M2 macrophages. Along with adipose tissue, immune cells, liver, brain, muscles and pancreas also suffers undergoes inflammatory damage. The inflammatory kinases like JNK and IKK apart from inhibiting insulin action and glucose uptake, also down-regulate transcriptional process resulting in increased expression of pro-inflammatory cytokines. The inflammatory process is initiated by Macrophage-like Kupffer cells following the transducer signals produced by the white adipose tissues further leading to necro-inflammation. Muscle fibre is said to suffer from decreased glycogen synthesis. Obesity also triggers the hypothalamic-pituitary adrenal axis. Pancreas modulating the insulin homeostasis and glucose tolerance is also exaggeratedly affected. Multi-dimensional interventions so as to check obesity induced metaflammation have been undertaken that includes therapeutic intervention and administration of synthetic drugs to target the actual inflammatory. Thus, by proper weight management and diet inflammatory responses in obesity can be controlled to a large extent.