Novel C-C chemokine receptor 2 antagonists in metabolic disease: a review of recent developments

Abstract

Introduction: C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, and its receptor, C-C chemokine receptor 2 (CCR2), play important roles in various inflammatory diseases. Recently, it has been reported that the CCL2/CCR2 pathway also has an important role in the pathogenesis of metabolic syndrome through its association with obesity and related systemic complications. Areas covered: This review focuses on the roles of CCR2 in the pathogenesis of adipose tissue inflammation and other organ damage associated with metabolic syndrome, which is still a matter of debate in many studies. It also covers the use of novel CCR2 antagonists as therapies in such conditions. Expert opinion: There is abundant experimental evidence that the CCL2/CCR2 pathway may be involved in chronic low-grade inflammation of adipose tissue in obesity and related metabolic diseases. Although animal models of diabetes and obesity, as well as human trials, have produced controversial results, there is continued interest in the roles of CCR2 inhibition in metabolic disease. Further identification of the mechanisms for recruitment and activation of phagocytes and determination of the roles of other chemokines are needed. Future study of these fundamental questions will provide a clearer understanding of adipose tissue biology and potential therapeutic targets for treatment of obesity-related metabolic disease, including diabetic nephropathy.