Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.
Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here we investigate the hypothesis that FD causes divergent changes in A2 AMPK activity in E- vs. oil (O)-implanted ovariectomized female rats, alongside dissimilar adjustments in circulating metabolic fuel (glucose, free fatty acids [FFA]) and energy deficit-sensitive hormone (corticosterone, glucagon, leptin) levels. FD decreased blood glucose in oil (O)- but not E-implanted ovariectomized female rats and elevated and reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. Western blot analysis of laser-microdissected A2 neurons showed that glucocorticoid receptor type II and very-long-chain acyl-CoA synthetase 3 protein profiles were amplified in FD/E vs. FD/O. A2 total AMPK protein was elevated without change in activity in FD/O, whereas FD/E exhibited increased AMPK activation along with decreased upstream phosphatase expression. The catecholamine biosynthetic enzyme dopamine-β-hydroxylase (DβH) was increased in FD/O but not FD/E A2 cells. The data show discordance between A2 AMPK activation and glycemic responses to FD; sensor activity was refractory to glucose decrements in FD/O but augmented in FD/E despite stabilized glucose and elevated FFA levels. E-dependent amplification of AMPK activity may reflect adaptive conversion to fatty acid oxidation and/or glucocorticoid stimulation. FD augmentation of A2 DβH protein profiles in FD/O but not FD/E animals suggests that FD may correspondingly regulate NE synthesis vs. metabolism/release in the absence vs. presence of E. Mechanisms underlying translation of E-contingent A2 neuron responses to FD into regulatory signaling remain to be determined. © 2016 Wiley Periodicals, Inc.
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana.
Karen P
KP
Briski
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana.
Fahaad S H
FSH
Alenazi
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana.
Manita
M
Shakya
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana.
Paul W
PW
Sylvester
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004343:Drug Implants / Q000008:administration & dosage; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism*
D004343:Drug Implants; D005230:Fatty Acids, Nonesterified; D018341:Receptors, Adrenergic, alpha-2; D004958:Estradiol; D006005:Phosphorylases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D000241:Adenosine
A2 noradrenergic neurons; adenosine 5′-monophosphate-activated protein kinase; corticosterone; estradiol; free fatty acid levels; glucocorticoid receptor; very-long-chain acyl-CoA synthetase 3