Ghrelin signaling of NPY/AgRP neurons in the hypothalamus in response to ICV injection of ghrelin in LP rats. Active ghrelin binds to its receptor GHSR and activates Gαq and PLC
β, which produces second messenger IP3. IP3 induces the release of calcium from ER, which activates (CAMKK2) by binding to CAM. CAMKK2 phosphorylates AMPK
α at Threonine 172, which then phosphorylates ACC at Serine 79. Phosphorylated ACC results in enhanced fatty acid metabolism and associated production of ROS, which stimulates the expression of Ucp2, Npy, and Agrp, and finally, diet intake. After ICV injection of ghrelin, phosphorylation of both AMPK and ACC was lower in LP rats compared to that of CT rats (expressed in bold minus sign), but expression of Npy and Agrp was higher in LP rats (expressed in bold plus sign). GHSR, growth hormone secretagogue type 1a receptor; NPY, neuropeptide Y; AgRP, Agouti‐related peptide; Gαq, G protein alpha q subunit; PLC
β, phospholipase C, beta; IP3, inositol triphosphate; ER, endoplasmic reticulum; CAMKK2, calcium/calmodulin‐dependent protein kinase kinase 2; CAM, calmodulin; AMPK, AMP activated protein kinase; ACC, acetyl‐CoA carboxylase; ROS, radical oxygen species; Ucp2, uncoupled protein 2.