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1.
Neuroscience ; 314: 35-46, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26628404

RESUMO

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.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ingestão de Alimentos , Estradiol/fisiologia , Hipotálamo/enzimologia , Neuropeptídeos/metabolismo , Norepinefrina/metabolismo , Rombencéfalo/enzimologia , Trifosfato de Adenosina/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Estradiol/administração & dosagem , Feminino , Hipotálamo/efeitos dos fármacos , Injeções Intraventriculares , Neuropeptídeo Y/metabolismo , Orexinas/metabolismo , Pró-Opiomelanocortina/metabolismo , Ratos , Ratos Sprague-Dawley , Rombencéfalo/efeitos dos fármacos , Fator Esteroidogênico 1/metabolismo
2.
Neuroscience ; 284: 888-899, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25446360

RESUMO

Dorsal vagal complex (DVC) AMPK regulation of food intake in the estradiol-treated ovariectomized (OVX) female rat is energy state-dependent. Here, RT-PCR array technology was used to identify estradiol-sensitive AMPK-regulated DVC signal transduction pathways that exhibit differential reactivity to sensor activation during energy balance versus imbalance. The AMP mimetic AICAR correspondingly reduced or stimulated cDVC phosphoAMPK (pAMPK) and estrogen receptor-beta (ERß) proteins in full-fed (F) versus 12-h food-deprived (D) estradiol-treated ovariectomized (OVX) rats, but elevated ER-alpha (ERα) in F only. Estradiol suppressed DVC ERß protein and hypoxia, NFκB, STAT3, STAT6, and Hedgehog signaling pathway marker genes against oil-implanted OVX controls. F+(A)ICAR and D+(S)aline groups each exhibited further inhibition of NFκB, STAT3, and Hedgehog pathway genes, and diminished PPAR, Notch, and STAT5 transcripts versus F+S. Conversely, genes in these six pathways were up-regulated by AICAR treatment of D. Results show that in this animal model, acute AMP augmentation or feeding cessation each inhibit both pAMPK and ERß expression, but in combination increase these protein profiles. pAMPK protein and DVC TNF (NFκB), SOCS3 (JAK/STAT), WNT6 (Hedgehog), and FABP1 (PPAR) mRNAs were down- or upregulated in parallel by AICAR in F versus D states, respectively. Further research is needed to determine the impact of ERß on opposing directionality of these responses, and to characterize the role of the aforementioned signaling pathways in hyperphagic responses in the female to AICAR-induced DVC AMPK activation during acute interruption of feeding.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ingestão de Alimentos/fisiologia , Estradiol/metabolismo , Estrogênios/metabolismo , Privação de Alimentos/fisiologia , Rombencéfalo/fisiologia , Animais , Ingestão de Alimentos/efeitos dos fármacos , Estradiol/administração & dosagem , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/farmacologia , Feminino , Ovariectomia , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Rombencéfalo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
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