scholarly journals Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism

2021 ◽  
Vol 22 (2) ◽  
pp. 759
Author(s):  
Karen P. Briski ◽  
Mostafa M. H. Ibrahim ◽  
A. S. M. Hasan Mahmood ◽  
Ayed A. Alshamrani
Keyword(s):  
Alternative Energy ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Receptor Expression ◽  
Hypothalamic Nucleus ◽  
Control Structures ◽  
Ventromedial Hypothalamic Nucleus ◽  
Glycogen Reserve ◽  
Noradrenergic Modulation ◽  
The Brain

The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with key glucostatic control structures in the brain, including the ventromedial hypothalamic nucleus (VMN). In the brain, the glycogen reserve is maintained within the astrocyte cell compartment as an alternative energy source to blood-derived glucose. VMN astrocytes are direct targets for metabolic stimulus-driven noradrenergic signaling due to their adrenergic receptor expression (AR). The current review discusses recent affirmative evidence that neuro-metabolic stability in the VMN may be shaped by NE influence on astrocyte glycogen metabolism and glycogen-derived substrate fuel supply. Noradrenergic modulation of estrogen receptor (ER) control of VMN glycogen phosphorylase (GP) isoform expression supports the interaction of catecholamine and estradiol signals in shaping the physiological stimulus-specific control of astrocyte glycogen mobilization. Sex-dimorphic NE control of glycogen synthase and GP brain versus muscle type proteins may be due, in part, to the dissimilar noradrenergic governance of astrocyte AR and ER variant profiles in males versus females. Forthcoming advances in the understanding of the molecular mechanistic framework for catecholamine stimulus integration with other regulatory inputs to VMN astrocytes will undoubtedly reveal useful new molecular targets in each sex for glycogen mediated defense of neuronal metabolic equilibrium during neuro-glucopenia.

scholarly journals Sex-dimorphic neuroestradiol regulation of ventromedial hypothalamic nucleus glucoregulatory transmitter and glycogen metabolism enzyme protein expression in the rat

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Md. Main Uddin ◽  
Mostafa M. H. Ibrahim ◽  
Karen P. Briski
Keyword(s):  
Protein Expression ◽  
Glycogen Synthase ◽  
Metabolic Stress ◽  
Glycogen Metabolism ◽  
Female Rats ◽  
Hypothalamic Nucleus ◽  
Energy Yield ◽  
Intact Male ◽  
Energy Deficiency ◽  
Ventromedial Hypothalamic Nucleus

Abstract Background Ventromedial hypothalamic nucleus (VMN) gluco-regulatory transmission is subject to sex-specific control by estradiol. The VMN is characterized by high levels of aromatase expression. Methods The aromatase inhibitor letrozole (LZ) was used with high-resolution microdissection/Western blot techniques to address the hypothesis that neuroestradiol exerts sex-dimorphic control of VMN neuronal nitric oxide synthase (nNOS) and glutamate decarboxylase65/67 (GAD) protein expression. Glycogen metabolism impacts VMN nNOS and GAD profiles; here, LZ treatment effects on VMN glycogen synthase (GS) and phosphorylase brain- (GPbb; glucoprivic-sensitive) and muscle (GPmm; norepinephrine-sensitive) variant proteins were examined. Results VMN aromatase protein content was similar between sexes. Intracerebroventricular LZ infusion of testes-intact male and ovariectomized, estradiol-replaced female rats blocked insulin-induced hypoglycemic (IIH) up-regulation of this profile. LZ exerted sex-contingent effects on basal VMN nNOS and GAD expression, but blocked IIH-induced NO stimulation and GAD suppression in each sex. Sex-contingent LZ effects on basal and hypoglycemic patterns of GPbb and GPmm expression occurred at distinctive levels of the VMN. LZ correspondingly down- or up-regulated baseline pyruvate recycling pathway marker protein expression in males (glutaminase) and females (malic enzyme-1), and altered INS effects on those proteins. Conclusions Results infer that neuroestradiol is required in each sex for optimal VMN metabolic transmitter signaling of hypoglycemic energy deficiency. Sex differences in VMN GP variant protein levels and sensitivity to aromatase may correlate with sex-dimorphic glycogen mobilization during this metabolic stress. Neuroestradiol may also exert sex-specific effects on glucogenic amino acid energy yield by actions on distinctive enzyme targets in each sex.

scholarly journals Steroidogenic Factor 1 Regulates Expression of the Cannabinoid Receptor 1 in the Ventromedial Hypothalamic Nucleus

2008 ◽  
Vol 22 (8) ◽  
pp. 1950-1961 ◽  
Author(s):  
Ki Woo Kim ◽  
Young-Hwan Jo ◽  
Liping Zhao ◽  
Nancy R. Stallings ◽  
Streamson C. Chua ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Cannabinoid Receptor ◽  
Hypothalamic Nucleus ◽  
Cannabinoid Receptor 1 ◽  
Steroidogenic Factor 1 ◽  
Ventromedial Hypothalamic Nucleus ◽  
Hypothalamic Slice ◽  
Responsive Element ◽  
And Function ◽  
The Brain

Abstract The nuclear receptor steroidogenic factor 1 (SF-1) plays essential roles in the development and function of the ventromedial hypothalamic nucleus (VMH). Considerable evidence links the VMH and SF-1 with the regulation of energy homeostasis. Here, we demonstrate that SF-1 colocalizes in VMH neurons with the cannabinoid receptor 1 (CB1R) and that a specific CB1R agonist modulates electrical activity of SF-1 neurons in hypothalamic slice preparations. We further show that SF-1 directly regulates CB1R gene expression via a SF-1-responsive element at −101 in its 5′-flanking region. Finally, we show that knockout mice with selective inactivation of SF-1 in the brain have decreased expression of CB1R in the region of the VMH and exhibit a blunted response to systemically administered CB1R agonists. These studies suggest that SF-1 directly regulates the expression of CB1R, which has been implicated in the regulation of energy homeostasis and anxiety-like behavior.

Ventromedial Hypothalamic Nucleus Glycogen Regulation of Metabolic-Sensory Neuron AMPK and Neurotransmitter Expression: Role of Lactate

2021 ◽  
Author(s):  
Khaggeswar Bheemanapally ◽  
Mostafa M.H. Ibrahim ◽  
Ayed Alshamrani ◽  
Karen P. Briski
Keyword(s):  
Nitric Oxide ◽  
Glycogen Metabolism ◽  
Female Rats ◽  
Hypothalamic Nucleus ◽  
Gamma Aminobutyric Acid ◽  
Ventromedial Hypothalamic Nucleus ◽  
Gaba Neuron ◽  
Amp Activated Protein Kinase ◽  
Corticosterone Release ◽  
Lactate Infusion

Astrocyte glycogen is dynamically remodeled during metabolic stability and provides oxidizable L-lactate equivalents during neuro-glucopenia. Current research investigated the hypothesis that ventromedial hypothalamic nucleus (VMN) glycogen metabolism controls gluco-stimulatory nitric oxide (NO) and/or gluco-inhibitory gamma-aminobutyric acid (GABA) neuron 5'-AMP-activated protein kinase (AMPK) and transmitter marker, e.g. neuronal nitric oxide synthase (nNOS), glutamate decarboxylase65/67 (GAD) protein expression. Adult ovariectomized estradiol-implanted female rats were injected into the VMN with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) before vehicle or L-lactate infusion. Western blot analysis of laser-catapult-microdissected nitrergic and GABAergic neurons showed that DAB caused lactate-reversible up-regulation of nNOS and GAD proteins. DAB suppressed or increased total AMPK content of NO and GABA neurons, respectively, by lactate-independent mechanisms, but lactate prevented drug enhancement of pAMPK expression in nitrergic neurons. Inhibition of VMN glycogen disassembly caused divergent changes in counter-regulatory hormone, e.g. corticosterone (increased) and glucagon (decreased) secretion. Outcomes show that VMN glycogen metabolism controls local gluco-regulatory transmission by means of lactate signal volume. Results implicate glycogen-derived lactate deficiency as a physiological stimulus of corticosterone release. Concurrent normalization of nitrergic neuron nNOS and pAMPK protein and corticosterone secretory response to DAB by lactate infers that the hypothalamic-pituitary-adrenal axis may be activated by VMN NO-mediated signals of cellular energy imbalance.

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