Hindbrain estrogen receptor regulation of ventromedial hypothalamic glycogen metabolism and glucoregulatory transmitter expression in the hypoglycemic male rat

Ali, Md. Haider; Napit, Prabhat R.; Mahmood, Akhtar; Bheemanapally, Khaggeswar; Alhamami, Hussain N.; Uddin, Md. Main; Mandal, Santosh K.; Ibrahim, Mostafa M.H.; Briski, Karen P.

doi:10.1016/j.neuroscience.2019.03.053

Cited by 17 publications

(8 citation statements)

References 19 publications

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“…The ability of lactate to prevent DAB suppression of A2 nerve cell estrogen receptor-alpha (ERα) and G-protein-coupled estrogen receptor-1 (GPER) protein content advances the novel notion that glycogen-derived energy fuel supply may control estradiol input to these neurons. The latter findings align with reports that hindbrain ERα and ER-beta (ERβ) regulate hypoglycemic patterns of the VMN transmitter and glycogen metabolic protein expression albeit differently in each sex [ 56 , 57 ]. Interestingly, we found that lactate abolished the DAB up-regulation of the VMN GPbb content but did not modify the drug effects on GPmm protein profiles.…”

Section: Ne Signaling Appraises the Vmn Of Hindbrain Glycogen Metasupporting

confidence: 90%

“…In recent work, we used a hypothalamic astrocyte primary cell culture model [ 58 ] to address the premise that dosage-contingent NE effects on astrocyte GS and GP isoform protein expression and glycogen accumulation may correlate with differential patterns of the AR variant expression. Modes of hindbrain noradrenergic signaling of metabolic deficiency evidently differed between sexes, as systemic hypoglycemia increased the VMN NE content in males [ 56 ] but diminished these levels in the females [ 57 ]. These sex-specific hypoglycemic patterns of NE input to the VMN imposed control of glycogen metabolism as hindbrain 6OHDA lesions alter hypoglycemia-associated GS and GP isoform protein expression [Briski, personal communication].…”

Section: Concentration-dependent Noradrenergic Regulation Of Hypotmentioning

confidence: 99%

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Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism

Briski

Ibrahim

Mahmood

et al. 2021

IJMS

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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.

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Section: Ne Signaling Appraises the Vmn Of Hindbrain Glycogen Metasupporting

confidence: 90%

Section: Concentration-dependent Noradrenergic Regulation Of Hypotmentioning

confidence: 99%

Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism

Briski

Ibrahim

Mahmood

et al. 2021

IJMS

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“…no. ABN904; MilliporeSigma, Burlington, MA), as described (Ali et al, 2019;Briski and Mandal, 2019;Napit et al, 2019). Membranes were incubated for 1 h with a peroxidase-conjugated goat anti-rabbit (NEF812001EA, 1:5,000; PerkinElmer, Waltham, MA) secondary antiserum prior to exposure to Supersignal West Femto maximum sensitivity chemiluminescent substrate (prod.…”

Section: Western Blot Analysis Of Vmn Glycogen Enzyme Protein Expressionmentioning

confidence: 99%

Hindbrain metabolic deficiency regulates ventromedial hypothalamic nucleus glycogen metabolism and glucose-regulatory signaling

Briski¹,

Mandal²

2020

Acta Neurobiologiae Experimentalis

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The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with downstream gluco-regulatory loci, including the ventromedial hypothalamic nucleus (VMN). Exogenous NE up-regulates VMN expression of glutamate decarboxylase (GAD), biomarker for the gluco-inhibitory transmitter γ-aminobutryic acid (GABA). Brain glycogen phosphorylase (GP)-muscle (GPmm) and -brain (GPbb) variants are stimulated in vitro by NE or energy deficiency, respectively. Current research investigated whether lactoprivic-driven VMN NE signaling regulates GABA and if VMN GPmm and GPbb profiles react differently to that deficit cue. Male rats were pretreated by caudal fourth ventricle delivery of the selective catecholamine neurotoxin 6-hydroxydopamine (6OHDA) ahead of the monocarboxylate transporter inhibitor alpha-cyano-4-hydroxycinnamic acid (4CIN). Micropunch-dissected VMN tissue was analyzed by Western blot and ELISA to assess NE-dependent 4CIN regulation of GAD and GP variant protein expression and NE activity. 4CIN caused 6OHDA-reversible augmentation of VMN NE content and plasma glucose and counter-regulatory hormone levels. 6OHDA stimulated basal VMN GAD expression, but prevented 4CIN stimulation of this profile. Neurotoxin inhibited or increased baseline VMN GPmm and GPbb levels, respectively, in non-4CIN-injected rats. 6OHDA deterred 4CIN inhibition of GPmm, but did not prevent drug stimulation of GPbb. Results affirm hindbrain lactoprivic regulation of glucostasis. Hindbrain NE exerts opposite effects on VMN GABA transmission during hindbrain lactostasis vs. -privation. VMN norepinephrine-vs. energy-sensitive GP variants are subject to dissimilar NE regulation during energy homeostasis, and respond differently to hindbrain lactoprivation.

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“…The other key places for action of estrogens are characterized by containing ERs and are found throughout the whole body[ 336 ]; but WAT[ 337 ], liver[ 338 ], muscle[ 339 ], and, essentially the brain[ 340 , 341 ] are the main targets for their actions, and are, at least, the best studied. ERβ globally regulates lipid homeostasis[ 145 ], its activation in obesity increases whole body metabolism and mitochondrial biogenesis as a countermeasure to excess WAT lipid storage[ 312 ].…”

Section: Introductionmentioning

confidence: 99%

Estrogens and the regulation of glucose metabolism

Alemany¹

2021

WJD

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The main estrogens: estradiol, estrone, and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions. However, their main effect in the body is probably the sustained control of core energy metabolism. Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses, and largely explain gender and age differences in energy metabolism: part of these mechanisms is already sufficiently known to justify both. With regard to energy, the estrogen molecular species act essentially through four key functions: (1) Facilitation of insulin secretion and control of glucose availability; (2) Modulation of energy partition, favoring the use of lipid as the main energy substrate when more available than carbohydrates; (3) Functional protection through antioxidant mechanisms; and (4) Central effects (largely through neural modulation) on whole body energy management. Analyzing the different actions of estrone, estradiol and their acyl esters, a tentative classification based on structure/effects has been postulated. Either separately or as a group, estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules. As a group, they constitute a powerful synergic action complex. In consequence, estrogens may be considered wardens of energy homeostasis.

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Hindbrain estrogen receptor regulation of ventromedial hypothalamic glycogen metabolism and glucoregulatory transmitter expression in the hypoglycemic male rat

Cited by 17 publications

References 19 publications

Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism

Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism

Hindbrain metabolic deficiency regulates ventromedial hypothalamic nucleus glycogen metabolism and glucose-regulatory signaling

Estrogens and the regulation of glucose metabolism

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