title: AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats.
abstract: AMP-activated protein kinase (AMPK) is an energy sensor that is activated by the increase of intracellular AMP:ATP ratio. AMPK in the hypothalamic arcuate nucleus (ARC) is activated during fasting and the activation of AMPK stimulates food intake. To clarify the pathway underlying AMPK-induced feeding, we monitored the activity of single ARC neurons by measuring cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2 fluorescence imaging. An AMPK activator, AICA-riboside (AICAR), at 200 μM increased [Ca(2+)](i) in 24% of ARC neurons. AMPK and acetyl CoA carboxylase were phosphorylated in the neurons with [Ca(2+)](i) responses to AICAR. AICAR-induced [Ca(2+)](i) increases were inhibited by Ca(2+)-free condition but not by thapsigargin, suggesting that AICAR increases [Ca(2+)](i) through Ca(2+) influx from extracellular space. Among AICAR-responding ARC neurons, 38% were neuropeptide Y (NPY)-immunoreactive neurons while no proopiomelanocortin (POMC)-immunoreactive neuron was observed. Intracerebroventricular administration of AICAR increased food intake, and the AICAR-induced food intake was abolished by the co-administration of NPY Y1 receptor antagonist, 1229U91. These results indicate that the activation of AMPK leads to the activation of ARC NPY neurons through Ca(2+) influx, thereby causing NPY-dependent food intake. These mechanisms could be implicated in the stimulation of food intake by physiological orexigenic substances.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohno
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sone
authors.forename: Shigeyasu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kurita
authors.forename: Darambazar
authors.initials: D
authors.lastname: Gantulga
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism / Q000502:physiology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D012265:Ribonucleotides / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C097287:1229U91; D009478:Neuropeptide Y; D010456:Peptides, Cyclic; D017476:Receptors, Neuropeptide Y; D012265:Ribonucleotides; C097212:neuropeptide Y-Y1 receptor; D000620:Aminoimidazole Carboxamide; D011333:Pro-Opiomelanocortin; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D002118:Calcium