Fig. 2.

Leptin/adiponectin balance in obesity. Leptin and adiponectin are two adipokines produced by adipose tissue. Leptin levels rise in obesity, while adiponectin falls. Leptin binds to a growth factor receptor at the cell surface, and promotes cell proliferation/opposes cell death by a variety of mechanisms. These include promoting cell growth (via stimulation of mTOR), angiogenesis and metastasis, while at the same time inhibiting antitumour mechanisms such as apoptosis and immune surveillance. Overall, therefore, the actions of leptin are pro-tumorigenic. Adiponectin, in contrast, binds to a G-protein coupled receptor at the cell surface, and broadly opposes these actions of leptin, by activating kinases such as AMP kinase (which decreases mTOR activity) and protein kinase A (which decreases angiogenesis). Normally the actions of these two hormones are balanced, to maintain cell proliferation at an appropriate rate, but in obesity leptin concentrations rise, and adiponectin falls, promoting a tumorigenic environment