title: Energy status determines hindbrain signal transduction pathway transcriptional reactivity to AMPK in the estradiol-treated ovariectomized female rat.
abstract: 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 (ERβ) 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 ERβ 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 ERβ 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 ERβ 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.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, 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, University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: F S H
authors.initials: FSH
authors.lastname: Alenazi
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, 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*; D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D010052:Ovariectomy; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D004958:Estradiol; D055372:AMP-Activated Protein Kinases
keywords: AICAR; dorsal vagal complex; estradiol; estrogen receptor-alpha; estrogen receptor-beta; hedgehog