Inflammation Resolution and Its Relevance to Metabolic Syndrome

Metabolic syndrome is a cluster of conditions including increased blood pressure, blood sugar, body fat, and cholesterolCholesterol or triglyceride levels. Metabolic syndrome increases the risk of heart disease, stroke, type 2 diabetes, fatty liver disease, atherosclerosisAtherosclerosis, neuro-degenerative diseases, airway disease and some cancers. Inflammation and metabolic syndrome are highly integrated and interdependent. Chronic low-grade inflammation is causal and also sequential to metabolic syndrome. Obesity stimulatesProinflammatory macrophages proinflammatory macrophagesMacrophage and cytokinesFunctions of brown adipose tissuecytokines that further deteriorates metabolic derangements. Inadequacy of insulin, leptinLeptin, resistin, adiponectinAdiponectin, and FGF, or resistance to their effect is caused by chronic low-grade inflammation. Knockout studies in preclinical species as well as pharmacological inhibition of inflammatory pathways in rodents and humans have demonstrated reversal of genetically- or diet-induced obesity and insulin resistance. NF-κβ and NF-κβ–sensitive genes Tbk1 and Ikbke induce metabolic abnormalities, which can be reversed by amlexanoxAmlexanox, an inhibitor of Tbk1 and Ikbke. Elevated circulating complement factor C3, due to terminal and alternative complement pathway activation is also linked to insulin resistance, diabetes, obesity, and atherosclerosisAtherosclerosis. Thus, strategies aimed at inflammation resolution hold promise for the prevention and treatment of metabolic syndromeTreatment of metabolic syndrome. This chapter highlights the significance of targeting inflammatory pathways for the prevention and treatment of metabolic syndromeTreatment of metabolic syndrome.