Fig. 6

Schematic of the mechanism of this work. When the leptin pathway is intact, binding of leptin to LEPR activates JAK2-STAT3 to promote FAO or activate IRS1/2-PI3K/AKT to mediate GLUT4 translocation on cell membranes to regulating glucose uptake through its receptor. However, the above pathways will be damaged under leptin receptor deficiency, which leads to obesity and diabetes. RYGB surgery activates AMPK and upregulates the cell membrane translocation of GLUT4, thus promoting cellular glucose uptake, while AMPK cannot trans-autophosphorylate STAT3 through the tyrosine site on LEPR in db/db mice through JAK2 due to the lack of leptin receptor. RYGB: Roux-en-Y gastric bypass; LEPR: leptin receptor; GLUT4: glucose transporter 4