Adipocytokines mediate pancreatic cancer tumorigenesis by different signaling mechanisms. a. Adiponectin secreted from adipose tissue binds to its receptor (AdipoR) to activate AKT, MAPK and AMPK pathways, which block the apoptosis of pancreatic cancer cells. b. Similarly, leptin binding to its receptor (OBR) results in activation of the JAK2/STAT3 pathway, which leads to matrix metalloproteinase-13 activation and eventual pancreatic cancer metastasis. In addition, OBR also regulates its own expression through hypoxia inducible factor-1, resulting in cancer cell survival via an unknown mechanism. Moreover, leptin also triggers Notch receptor signaling, which results in activation of its downstream molecules (survivin and Hey2), thereby increasing cancer cell proliferation.