title: Role of estradiol in intrinsic hindbrain AMPK regulation of hypothalamic AMPK, metabolic neuropeptide, and norepinephrine activity and food intake in the female rat.
abstract: This study addressed the hypothesis that dorsomedial hindbrain adenosine 5'-monophosphate-activated protein kinase (AMPK) imposes inherent estradiol-dependent control of hypothalamic AMPK, neuropeptide, and norepinephrine (NE) activity and feeding in the female rat. Estradiol (E)- or oil (O)-implanted ovariectomized rats were injected with the AMPK inhibitor compound c (Cc) or vehicle into the caudal fourth ventricle (CV4) prior to micropunch-dissection of individual hypothalamic metabolic loci or assessment of food intake. Cc decreased hindbrain dorsal vagal complex phosphoAMPK (pAMPK) in both E and O; tissue ATP levels were reduced by this treatment in O only. In E/Cc, pAMPK expression was diminished in the lateral hypothalamic area (LHA) and ventromedial (VMH) and paraventricular (PVH) nuclei; only PVH pAMPK was suppressed by this treatment in O/Cc. Cc decreased PVH corticotropin-releasing hormone and arcuate (ARH) proopiomelanocortin (POMC) and neuropeptide Y in O, but suppressed only POMC in E. O/Cc exhibited both augmented (PVH, VMH) and decreased (LHA, ARH) hypothalamic NE content, whereas Cc treatment of E elevated preoptic and dorsomedial hypothalamic nucleus NE. Cc completely or incompletely repressed feeding in E versus O, respectively. Results implicate dorsomedial hindbrain AMPK in physiological stimulus-induced feeding in females. Excepting POMC, hypothalamic neuropeptide responses to this sensor may be contingent on estrogen. Estradiol likely designates hypothalamic targets of altered NE signaling due to hindbrain AMPK activation. Divergent changes in NE content of hypothalamic loci in O/Cc uniquely demonstrate sensor-induced bimodal catecholamine signaling to those sites.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: F S H
authors.initials: FS
authors.lastname: Alenazi
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: B A
authors.initials: BA
authors.lastname: Ibrahim
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: H
authors.initials: H
authors.lastname: Al-Hamami
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: M
authors.initials: M
authors.lastname: Shakiya
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States. Electronic address: briski@ulm.edu.
authors.forename: K P
authors.initials: KP
authors.lastname: Briski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D007276:Injections, Intraventricular; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects / Q000201:enzymology*; D054339:Steroidogenic Factor 1 / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D054339:Steroidogenic Factor 1; C515060:steroidogenic factor 1, rat; D004958:Estradiol; D011333:Pro-Opiomelanocortin; D000255:Adenosine Triphosphate; D003346:Corticotropin-Releasing Hormone; D055372:AMP-Activated Protein Kinases; D009638:Norepinephrine
keywords: ATP; adenosine 5′-monophosphate-activated protein kinase; compound C; estradiol; norepinephrine; pro-opiomelanocortin