The role of interleukin-6 in insulin resistance, body fat distribution and energy balance

Interleukin-6 (IL-6) is a central player in the regulation of inflammation, haematopoiesis, immune response and host defense mechanisms. During the last decade, an accumulating amount of data suggested a pivotal role for IL-6 in metabolic processes, thus fortifying the picture of IL-6 as a multifaceted, pleiotropic cytokine. Because of its secretion by adipose tissue and contracting skeletal muscle and its broad action on central and peripheral organs, IL-6 has been termed an adipokine and a myokine. Its quantitative release from adipose tissue results in a subclinical, systemic elevation of IL-6 plasma levels with increasing body fat content, which may be implicated in the proinflammatory state leading to insulin resistance. On the other hand, IL-6 produced in the working muscle during physical activity could act as an energy sensor by activating AMP-activated kinase and enhancing glucose disposal, lipolysis and fat oxidation. In addition, both impaired IL-6 secretion and action are risk factors for weight gain. Thus, IL-6 clearly has lipolytic effects and anti-obesity potential. However, the application of IL-6 itself is at least limited by a narrow therapeutic range and its important function for a balanced inflammatory response. Further studies on the molecular basis of the metabolic effects of IL-6 could elucidate novel therapeutic strategies for custom-designed, IL-6-related substances.