scholarly journals The brain needs interleukin-6 (IL-6) to maintain a “healthy” energy balance. Focus on “IL-6 ameliorates defective leptin sensitivity in DIO ventromedial hypothalamic nucleus neurons”

2016 ◽  
Vol 311 (6) ◽  
pp. R989-R991 ◽  
Author(s):  
Thomas A. Lutz
Keyword(s):  
Energy Balance ◽  
Interleukin 6 ◽  
Hypothalamic Nucleus ◽  
Leptin Sensitivity ◽  
Ventromedial Hypothalamic Nucleus ◽  
The Brain

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 Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity

2020 ◽  
Author(s):  
Jessica L. Cote ◽  
Lawrence S. Argetsinger ◽  
Anabel Flores ◽  
Alan C. Rupp ◽  
Joel M. Cline ◽  
...  
Keyword(s):  
Energy Balance ◽  
Adapter Protein ◽  
Wild Type ◽  
Leptin Sensitivity ◽  
High Fat Diets ◽  
Independent Mechanism ◽  
Alternatively Spliced ◽  
Fat Diets ◽  
The Brain ◽  
Inactivating Mutations

Mice lacking SH2B1 and humans with inactivating mutations of SH2B1 display severe obesity and insulin resistance. SH2B1 is an adapter protein that is recruited to the receptors of multiple hormones and neurotrophic factors. Of the four known alternatively-spliced SH2B1<i> </i>isoforms<i>,</i> SH2B1b and SH2B1g exhibit ubiquitous expression, whereas SH2B1a and SH2B1d are essentially restricted to the brain. To understand the roles for SH2B1a and SH2B1d in energy balance and glucose metabolism, we generated mice lacking these brain-specific isoforms (adKO mice). adKO mice exhibit decreased food intake, protection from weight gain on standard and high fat diets, and an adiposity-dependent improvement in glucose homeostasis. SH2B1 has been suggested to impact energy balance via the modulation of leptin action. However, adKO mice exhibit leptin sensitivity that is similar to that of wild-type mice by multiple measures. Thus, decreasing the abundance of SH2B1a and/or SH2B1d relative to the other SH2B1 isoforms likely shifts energy balance towards a lean phenotype via a primarily leptin-independent mechanism. Our findings suggest that the different alternatively-spliced isoforms of SH2B1 perform different functions <i>in</i> <i>vivo</i>. <br>

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.

scholarly journals Deletion of the brain-specific α and δ isoforms of adapter protein SH2B1 protects mice from obesity

2020 ◽  
Author(s):  
Ada Admin ◽  
Jessica L. Cote ◽  
Lawrence S. Argetsinger ◽  
Anabel Flores ◽  
Alan C. Rupp ◽  
...  
Keyword(s):  
Energy Balance ◽  
Adapter Protein ◽  
Wild Type ◽  
Leptin Sensitivity ◽  
High Fat Diets ◽  
Independent Mechanism ◽  
Alternatively Spliced ◽  
Fat Diets ◽  
The Brain ◽  
Inactivating Mutations

Mice lacking SH2B1 and humans with inactivating mutations of SH2B1 display severe obesity and insulin resistance. SH2B1 is an adapter protein that is recruited to the receptors of multiple hormones and neurotrophic factors. Of the four known alternatively-spliced SH2B1<i> </i>isoforms<i>,</i> SH2B1b and SH2B1g exhibit ubiquitous expression, whereas SH2B1a and SH2B1d are essentially restricted to the brain. To understand the roles for SH2B1a and SH2B1d in energy balance and glucose metabolism, we generated mice lacking these brain-specific isoforms (adKO mice). adKO mice exhibit decreased food intake, protection from weight gain on standard and high fat diets, and an adiposity-dependent improvement in glucose homeostasis. SH2B1 has been suggested to impact energy balance via the modulation of leptin action. However, adKO mice exhibit leptin sensitivity that is similar to that of wild-type mice by multiple measures. Thus, decreasing the abundance of SH2B1a and/or SH2B1d relative to the other SH2B1 isoforms likely shifts energy balance towards a lean phenotype via a primarily leptin-independent mechanism. Our findings suggest that the different alternatively-spliced isoforms of SH2B1 perform different functions <i>in</i> <i>vivo</i>. <br>

313-OR: PACAP from the Ventromedial Hypothalamic Nucleus Controls Both Energy Balance and Glucose Homeostasis

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 313-OR
Author(s):  
NADEJDA BOZADJIEVA ◽  
RACHEL A. ROSS ◽  
BRADFORD LOWELL ◽  
JONATHAN N. FLAK
Keyword(s):  
Energy Balance ◽  
Glucose Homeostasis ◽  
Hypothalamic Nucleus ◽  
Ventromedial Hypothalamic Nucleus

scholarly journals IL-6 ameliorates defective leptin sensitivity in DIO ventromedial hypothalamic nucleus neurons

2016 ◽  
Vol 311 (4) ◽  
pp. R764-R770 ◽  
Author(s):  
Louise Larsen ◽  
Christelle Le Foll ◽  
Ambrose A. Dunn-Meynell ◽  
Barry E. Levin
Keyword(s):  
Leptin Receptor ◽  
Cellular Level ◽  
Leptin Resistance ◽  
Hypothalamic Nucleus ◽  
Reduce Food Intake ◽  
Bardet Biedl Syndrome ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Ventromedial Hypothalamic Nucleus ◽  
Pancreatic Peptide

Rats selectively bred to develop diet-induced obesity (DIO) have an early onset reduction in the sensitivity of their ventromedial hypothalamic nucleus (VMN) neurons to leptin compared with diet-resistant (DR) rats. This reduced sensitivity includes decreased leptin receptor (Lepr-b) mRNA expression, leptin receptor binding, leptin-induced phosphorylation of STAT3 (pSTAT3), and impaired leptin excitation (LepE) of VMN neurons. When administered exogenously, the pancreatic peptide, amylin, acts synergistically to reduce food intake and body weight in obese, leptin-resistant DIO rats by increasing VMN leptin signaling, likely by stimulation of microglia IL-6, which acts on its receptor to increase leptin-induced pSTAT3. Here, we demonstrate that incubation of cultured VMN neurons of outbred rats with IL-6 increases their leptin sensitivity. Control, dissociated DIO VMN neurons express 66% less Lepr-b and 75% less Bardet Biedl Syndrome-6 (BBS6) mRNA and have reduced leptin-induced activation of LepE neurons compared with DR neurons. Incubation for 4 days with IL-6 increased DIO neuron Lepr-b expression by 77% and BBS6 by 290% and corrected their defective leptin activation of LepE neurons to DR levels. Since BBS6 enhances trafficking of Lepr-b to the cell membrane, the increases in Lepr-b and BBS6 expression appear to account for correction of the reduced leptin excitation of DIO LepE neurons to that of control DR rats. These data support prior findings suggesting that IL-6 mediates the leptin-sensitizing effects of amylin on VMN neurons and that the inherent leptin resistance of DIO rats can be effectively reversed at a cellular level by IL-6.

scholarly journals Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

2014 ◽  
Vol 307 (6) ◽  
pp. R737-R745 ◽  
Author(s):  
Emily E. Noble ◽  
Charles J. Billington ◽  
Catherine M. Kotz ◽  
ChuanFeng Wang
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Negative Regulator ◽  
Hypothalamic Nucleus ◽  
Sprague Dawley ◽  
Ventromedial Hypothalamic Nucleus ◽  
Oxytocin Receptors

Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin.

scholarly journals Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity

2020 ◽  
Author(s):  
Jessica L. Cote ◽  
Lawrence S. Argetsinger ◽  
Anabel Flores ◽  
Alan C. Rupp ◽  
Joel M. Cline ◽  
...  
Keyword(s):  
Energy Balance ◽  
Adapter Protein ◽  
Wild Type ◽  
Leptin Sensitivity ◽  
High Fat Diets ◽  
Independent Mechanism ◽  
Alternatively Spliced ◽  
Fat Diets ◽  
The Brain ◽  
Inactivating Mutations

Mice lacking SH2B1 and humans with inactivating mutations of SH2B1 display severe obesity and insulin resistance. SH2B1 is an adapter protein that is recruited to the receptors of multiple hormones and neurotrophic factors. Of the four known alternatively-spliced SH2B1<i> </i>isoforms<i>,</i> SH2B1b and SH2B1g exhibit ubiquitous expression, whereas SH2B1a and SH2B1d are essentially restricted to the brain. To understand the roles for SH2B1a and SH2B1d in energy balance and glucose metabolism, we generated mice lacking these brain-specific isoforms (adKO mice). adKO mice exhibit decreased food intake, protection from weight gain on standard and high fat diets, and an adiposity-dependent improvement in glucose homeostasis. SH2B1 has been suggested to impact energy balance via the modulation of leptin action. However, adKO mice exhibit leptin sensitivity that is similar to that of wild-type mice by multiple measures. Thus, decreasing the abundance of SH2B1a and/or SH2B1d relative to the other SH2B1 isoforms likely shifts energy balance towards a lean phenotype via a primarily leptin-independent mechanism. Our findings suggest that the different alternatively-spliced isoforms of SH2B1 perform different functions <i>in</i> <i>vivo</i>. <br>

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