Abstract
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.
Brackets indicating effects of short‐term food deprivation on A2 nerve cell total and phosphorylated AMPK protein content show that this metabolic challenge elevated total AMPK without altering in activity in ovariectomized (OVX) animals implanted with oil (right‐hand side), but augmented AMPK activation alongside decreased upstream phosphatase expression in OVX rats replaced with estradiol (left‐hand side).