The role of gp130 receptor cytokines in the regulation of metabolic homeostasis

Abstract

ABSTRACT It is well known that obesity is responsible, at least in part, for the increased incidence of chronic diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer. Despite public education programs emphasizing lifestyle modifications to arrest this global pandemic, it is now estimated that 10–15% of the world's population are overweight or obese. As a result, new therapeutic options for the treatment of obesity-related disorders are clearly warranted. Much of the benefit of physical activity has been attributed to several mechanisms including reduced adiposity, increased cardiorespiratory fitness, reduced circulating lipids and the maintenance of muscle mass. However, the observation that the gp130 receptor cytokine interleukin-6 (IL-6) was released from skeletal muscle during exercise to improve metabolic homeostasis altered our understanding of the health benefits of exercise and opened avenues for research into potential novel therapeutics to treat metabolic disease. One gp130 receptor cytokine in particular, ciliary neurotrophic factor (CNTF), a pluripotent neurocytokine, showed efficacy as a potential anti-obesogenic therapy. This review examines the potential of gp130 receptor ligands, with a focus on IL-6 and CNTF as therapeutic strategies to treat obesity-related disorders.