Clinical review: adiponectin biology and its role in inflammation and critical illness

Abstract

Adiponectin is an adipokine first described just over a decade ago. Produced almost exclusively by adipocytes, adiponectin circulates in high concentrations in human plasma. Research into this hormone has revealed it to have insulin-sensitizing, anti-inflammatory and cardioprotective roles. This review discusses the history, biology and physiological role of adiponectin and explores its role in disease, with specific focus on adiponectin in inflammation and sepsis. It appears that an inverse relationship exists between adiponectin and inflammatory cytokines. Low levels of adiponectin have been found in critically ill patients, although data are limited in human subjects at this stage. The role of adiponectin in systemic inflammation and critical illness is not well defined. Early data suggest that plasma levels of adiponectin are decreased in critical illness. Whether this is a result of the disease process itself or whether patients with lower levels of this hormone are more susceptible to developing a critical illness is not known. This observation of lower adiponectin levels then raises the possibility of therapeutic options to increase circulating adiponectin levels. The various options for modulation of serum adiponectin (recombinant adiponectin, thiazolidinediones) are discussed.

Figure 1

The structure and multimerization of adiponectin. (a) The domain structure of human adiponectin. (b) Adiponectin multimerization and analysis by velocity sedimentation. Separation of low-molecular weight (LMW) and high-molecular weight (HMW) multimers was performed by centrifugation on a 5 to 20% sucrose density gradient. Fractions 2 to 7 of the gradient contain the LMW multimers, while the HMW multimers are found in fractions 8 to 11. Reproduced from Whitehead JP and colleagues [5].

Figure 2

The anti-inflammatory actions of adiponectin. NK, natural killer.