Adipocytokines in obesity and metabolic disease

Abstract

The current global obesity pandemic is the leading cause for the soaring rates of metabolic diseases, especially diabetes, cardiovascular disease, hypertension, and non-alcoholic hepatosteatosis. Efforts devoted to find cures for obesity and associated disorders in the past two decades have prompted intensive interest in adipocyte biology, and have led to major advances in the mechanistic understanding of adipose tissue as an essential endocrine organ. Adipose tissue secretes an array of hormones (adipokines) that signal key organs to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. In addition, obesity induces production of inflammatory cytokines (often referred to together with adipokines as adipocytokines) and infiltration of immune cells into adipose tissue, which creates a state of chronic low-grade inflammation. Metabolic inflammation has been increasingly recognized as a unifying mechanism linking obesity to a broad spectrum of pathological conditions. This review focuses on classic examples of adipocytokines that have helped to form the basis of the endocrine and inflammatory roles of adipose tissue, and it also details a few newly characterized adipocytokines that provide fresh insights into adipose biology. Studies of adipocytokines in clinical settings and their therapeutic potential are also discussed.

Keywords: adipocyte; adipocytokine; adipokine; metabolic inflammation; obesity.

Figure 1. Adipocytokines and metabolic inflammation in adipose tissue

Adipocokines derived from adipose tissue are the results of intertwined interaction between adipocytes and immune cells that infiltrate adipose tissue. Adipocytokines mediate crosstalk among different cell populations within adipose tissue and also travel to remote organs to regulate systemic energy metabolism. The level and action of adipocytokines are often altered in obese subjects, which contributes to obesity-induced disorders.

Figure 2. aP2 as a lipid-activated adipokine

aP2 is secreted from adipocytes through a process that is regulated by fasting and lipolysis. Circulating aP2 acts on liver tissue to stimulate the gluconeogenic program and enhance hepatic glucose production. Other potential functions of aP2 in local adipose-macrophage interaction and on other metabolic organs warrant further investigation.