title: Central mechanisms involved in the orexigenic actions of ghrelin.
abstract: Ghrelin is a stomach hormone, secreted into the bloodstream, that initiates food intake by activating NPY/AgRP neurons in the hypothalamic acruate nucleus. This review focuses on recent evidence that details the mechanisms through which ghrelin activate receptors on NPY neurons and downstream signaling within NPY neurons. The downstream signaling involves a novel CaMKK-AMPK-CPT1-UCP2 pathway that enhances mitochondrial efficiency and buffers reactive oxygen species in order to maintain an appropriate firing response in NPY. Recent evidence that shows metabolic status affects ghrelin signaling in NPY is also described. In particular, ghrelin does not activate NPY neurons in diet-induced obese mice and ghrelin does not increase food intake. The potential mechanisms and implications of ghrelin resistance are discussed.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3183, Australia. Zane.andrews@monash.edu
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating; D004734:Energy Metabolism; D005215:Fasting / Q000009:adverse effects; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D054439:Ghrelin; D008565:Membrane Proteins; D009478:Neuropeptide Y; D054440:Receptors, Ghrelin; D000217:Acyltransferases; C526983:Mboat4 protein, mouse; D002118:Calcium