New perspectives on the NLRP3 inflammasome—colchicine and the suppression of inflammatory pathways in metabolic syndrome associated diseases

In the past decade, the metabolic syndrome has been recast as a chronic inflammatory disease whose mechanisms involve macrophage and neutrophil activation, initiation of the nod-like receptor protein 3 (NLRP3) inflammasome, and IL-1β secretion. Colchicine, an inhibitor of NLRP3, has been linked to the prevention or amelioration of diseases associated with the metabolic syndrome, including diabetes and cardiovascular disease. Its underlying therapeutic mechanisms extend beyond direct suppression of NLRP3, and include sirtuin and AMP-activated protein kinase (AMPK) pathway regulation, and downregulation of cellular stress signals, which promote atherosclerotic plaque rupture, insulin resistance, and obesity. Colchicine’s proven efficacy in preventing cardiovascular disease is a promising new development recognized by its inclusion in the 2023 American College of Cardiology treatment guidelines. As colchicine’s effects are better understood, along with a clearer understanding of metabolic syndrome’s pathophysiology, promising new applications and uses for this old drug may be on the horizon and are worthy of further investigation. In this review, we discuss colchicine’s pharmacology and explore its established and emerging anti-inflammatory mechanisms, and the role these could play in disrupting the chronic inflammation in metabolic syndrome and associated diseases.