JAK2 and Insulin resistance: Elevated leptin levels directly enhance the proliferative, invasive, and migratory capacities of CRC cells through activation of the Janus Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) and PI3K/AKT signaling pathways, while simultaneously suppressing adiponectin expression, exacerbating insulin resistance, and disrupting metabolic homeostasis (124).