Obesity is characterized by increased storage of
fatty acids in an expanded adipose tissue mass and is closely associated with the development of
insulin resistance in peripheral tissues such as skeletal muscle and the liver. In addition to being the largest source of fuel in the body, adipose tissue and resident macrophages are also the source of a number of secreted
proteins. Cloning of the obese gene and the identification of its product,
leptin, was one of the first discoveries of an adipocyte-derived signaling molecule and established an important role for adipose tissue as an endocrine organ. Since then,
leptin has been found to have a profound role in the regulation of whole-body metabolism by stimulating energy expenditure, inhibiting food intake and restoring euglycemia, however, in most cases of
obesity leptin resistance limits its biological efficacy. In contrast to
leptin,
adiponectin secretion is often diminished in
obesity.
Adiponectin acts to increase
insulin sensitivity,
fatty acid oxidation, as well as energy expenditure and reduces the production of
glucose by the liver.
Resistin and
retinol binding protein-4 are less well described. Their expression levels are positively correlated with adiposity and they are both implicated in the development of
insulin resistance. More recently it has been acknowledged that macrophages are an important part of the secretory function of adipose tissue and the main source of inflammatory cyokines, such as
TNFalpha and
IL-6. An increase in circulating levels of these macrophage-derived factors in
obesity leads to a chronic low-grade inflammatory state that has been linked to the development of
insulin resistance and diabetes. These
proteins commonly known as
adipokines are central to the dynamic control of energy metabolism, communicating the nutrient status of the organism with the tissues responsible for controlling both energy intake and expenditure as well as
insulin sensitivity.