scholarly journals Leptin receptor signaling in the lateral parabrachial nucleus contributes to the control of food intake

2014 ◽  
Vol 307 (11) ◽  
pp. R1338-R1344 ◽  
Author(s):  
Amber L. Alhadeff ◽  
Matthew R. Hayes ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Neural Control ◽  
Leptin Receptor ◽  
Sensory Information ◽  
Progressive Ratio ◽  
Meal Size ◽  
Parabrachial Nucleus ◽  
Lateral Parabrachial Nucleus ◽  
Site Of Action ◽  
Integral Role

Pontine parabrachial nucleus (PBN) neurons integrate visceral, oral, and other sensory information, playing an integral role in the neural control of feeding. Current experiments probed whether lateral PBN (lPBN) leptin receptor (LepRb) signaling contributes to this function. Intra-lPBN leptin microinjection significantly reduced cumulative chow intake, average meal size, and body weight in rats, independent of effects on locomotor activity or gastric emptying. In contrast to the effects observed following LepRb activation in other nuclei, lPBN LepRb stimulation did not affect progressive ratio responding for sucrose reward or conditioned place preference for a palatable food. Collectively, results suggest that lPBN LepRb activation reduces food intake by modulating the neural processing of meal size/satiation signaling, and highlight the lPBN as a novel site of action for leptin-mediated food intake control.

scholarly journals Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor

2015 ◽  
Vol 309 (8) ◽  
pp. E759-E766 ◽  
Author(s):  
Amber L. Alhadeff ◽  
Danielle Golub ◽  
Matthew R. Hayes ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Receptor Expression ◽  
Parabrachial Nucleus ◽  
Reticular Nucleus ◽  
Receptor Signaling ◽  
Y1 Receptor ◽  
Lateral Parabrachial Nucleus ◽  
Site Of Action ◽  
Sites Of Action

Although central PYY delivery potently increases food intake, the sites of action and mechanisms mediating these hyperphagic effects are not fully understood. The present studies investigate the contribution of lateral parabrachial nucleus (lPBN) PYY-Y receptor signaling to food intake control, as lPBN neurons express Y receptors and receive PYY fibers and are known to integrate circulating and visceral sensory signals to regulate energy balance. Immunohistochemical results identified a subpopulation of gigantocellular reticular nucleus PYY-producing neurons that project monosynaptically to the lPBN, providing an endogenous source of PYY to the lPBN. lPBN microinjection of PYY-(1–36) or PYY-(3–36) markedly increased food intake by increasing meal size. To determine which receptors mediate these behavioral results, we first performed quantitative real-time PCR to examine the relative levels of Y receptor expression in lPBN tissue. Gene expression analyses revealed that, while Y1, Y2, and Y5 receptors are each expressed in lPBN tissue, Y1 receptor mRNA is expressed at fivefold higher levels than the others. Furthermore, behavioral/pharmacological results demonstrated that the hyperphagic effects of PYY-(3–36) were eliminated by lPBN pretreatment with a selective Y1 receptor antagonist. Together, these results highlight the lPBN as a novel site of action for the intake-stimulatory effects of central PYY-Y1 receptor signaling.

scholarly journals Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2380-2392 ◽  
Author(s):  
Yang Liu ◽  
Ying Huang ◽  
Tiemin Liu ◽  
Hua Wu ◽  
Huxing Cui ◽  
...  
Keyword(s):  
Food Intake ◽  
Parabrachial Nucleus ◽  
Designer Drug ◽  
Male Mice ◽  
Moderate Dose ◽  
Related Peptide ◽  
Lateral Parabrachial Nucleus ◽  
Melanocortin 4 Receptor ◽  
Double Immunohistochemistry ◽  
Stimulation Of

Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.

scholarly journals Ghrelin in the lateral parabrachial nucleus influences the excitability of glucosensing neurons, increases food intake and body weight

2020 ◽  
Vol 9 (12) ◽  
pp. 1168-1177
Author(s):  
Caishun Zhang ◽  
Junhua Yuan ◽  
Qian Lin ◽  
Manwen Li ◽  
Liuxin Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Firing Rate ◽  
Body Weight Gain ◽  
Parabrachial Nucleus ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Lateral Parabrachial Nucleus

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR−/− mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR−/− mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

scholarly journals Ghrelin Receptor Stimulation of the Lateral Parabrachial Nucleus in Rats Increases Food Intake but not Food Motivation

Obesity ◽  
2020 ◽  
Vol 28 (8) ◽  
pp. 1503-1511
Author(s):  
Tina Bake ◽  
Marie V. Le May ◽  
Christian E. Edvardsson ◽  
Heike Vogel ◽  
Ulrika Bergström ◽  
...  
Keyword(s):  
Food Intake ◽  
Parabrachial Nucleus ◽  
Food Motivation ◽  
Receptor Stimulation ◽  
Ghrelin Receptor ◽  
Lateral Parabrachial Nucleus ◽  
Stimulation Of

scholarly journals Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals

2012 ◽  
Vol 303 (4) ◽  
pp. E496-E503 ◽  
Author(s):  
Scott E. Kanoski ◽  
Shiru Zhao ◽  
Douglas J. Guarnieri ◽  
Ralph J. DiLeone ◽  
Jianqun Yan ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Leptin Receptor ◽  
Nucleus Tractus Solitarius ◽  
Balance Control ◽  
Area Postrema ◽  
Meal Size ◽  
Receptor Signaling ◽  
Medial Nucleus ◽  
Neuronal Systems

Leptin receptor (LepRb) signaling in the hindbrain is required for energy balance control. Yet the specific hindbrain neurons and the behavioral processes mediating energy balance control by hindbrain leptin signaling are unknown. Studies here employ genetic [adeno-associated virally mediated RNA interference (AAV-RNAi)] and pharmacological methodologies to specify the neurons and the mechanisms through which hindbrain LepRb signaling contributes to the control of food intake. Results show that AAV-RNAi-mediated LepRb knockdown targeting a region encompassing the mNTS and area postrema (AP) (mNTS/AP LepRbKD) increases overall cumulative food intake by increasing the size of spontaneous meals. Other results show that pharmacological hindbrain leptin delivery and RNAi-mediated mNTS/AP LepRb knockdown increased and decreased the intake-suppressive effects of intraduodenal nutrient infusion, respectively. These meal size and intestinally derived signal amplification effects are likely mediated by LepRb signaling in the mNTS and not the AP, since 4th icv and mNTS parenchymal leptin (0.5 μg) administration reduced food intake, whereas this dose did not influence food intake when injected into the AP. Overall, these findings deepen the understanding of the distributed neuronal systems and behavioral mechanisms that mediate the effects of leptin receptor signaling on the control of food intake.

scholarly journals Functional and Neurochemical Identification of Ghrelin Receptor (GHSR)-Expressing Cells of the Lateral Parabrachial Nucleus in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Marie V. Le May ◽  
Fiona Peris-Sampedro ◽  
Iris Stoltenborg ◽  
Erik Schéle ◽  
Tina Bake ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Food Choice ◽  
Viral Vector ◽  
Sucrose Solution ◽  
Parabrachial Nucleus ◽  
Growth Hormone Secretagogue ◽  
Lateral Parabrachial Nucleus ◽  
Obesogenic Diet

The lateral parabrachial nucleus (lPBN), located in the pons, is a well-recognized anorexigenic center harboring, amongst others, the calcitonin gene-related peptide (CGRP)-expressing neurons that play a key role. The receptor for the orexigenic hormone ghrelin (the growth hormone secretagogue receptor, GHSR) is also abundantly expressed in the lPBN and ghrelin delivery to this site has recently been shown to increase food intake and alter food choice. Here we sought to explore whether GHSR-expressing cells in the lPBN (GHSRlPBN cells) contribute to feeding control, food choice and body weight gain in mice offered an obesogenic diet, involving studies in which GHSRlPBN cells were silenced. We also explored the neurochemical identity of GHSRlPBN cells. To silence GHSRlPBN cells, Ghsr-IRES-Cre male mice were bilaterally injected intra-lPBN with a Cre-dependent viral vector expressing tetanus toxin-light chain. Unlike control wild-type littermates that significantly increased in body weight on the obesogenic diet (i.e., high-fat high-sugar free choice diet comprising chow, lard and 9% sucrose solution), the heterozygous mice with silenced GHSRlPBN cells were resistant to diet-induced weight gain with significantly lower food intake and fat weight. The lean phenotype appeared to result from a decreased food intake compared to controls and caloric efficiency was unaltered. Additionally, silencing the GHSRlPBN cells altered food choice, significantly reducing palatable food consumption. RNAscope and immunohistochemical studies of the lPBN revealed considerable co-expression of GHSR with glutamate and pituitary adenylate cyclase-activating peptide (PACAP), and much less with neurotensin, substance P and CGRP. Thus, the GHSRlPBN cells are important for diet-induced weight gain and adiposity, as well as in the regulation of food intake and food choice. Most GHSRlPBN cells were found to be glutamatergic and the majority (76%) do not belong to the well-characterized anorexigenic CGRP cell population.

scholarly journals A novel cholinergic neural pathway and its role in the drug relapse

2021 ◽  
Author(s):  
Teng He ◽  
Wenwen Chen ◽  
Yu Fan ◽  
Xing Xu ◽  
Zilin Wang ◽  
...  
Keyword(s):  
Food Intake ◽  
Conditioned Place Preference ◽  
Choline Acetyltransferase ◽  
Aminobutyric Acid ◽  
Central Nucleus ◽  
Parabrachial Nucleus ◽  
Neural Pathway ◽  
Lateral Parabrachial Nucleus ◽  
Drug Relapse ◽  
Cholinergic Projection

The lateral parabrachial nucleus (LPB) is critical hub implicated in the control of food intake, reward and aversion. Here, we identified a novel cholinergic projection from choline acetyltransferase (ChAT)-positive neurons in external portion of the lateral parabrachial nucleus (eLPBChAT) to γ-aminobutyric acid (GABA) neurons in central nucleus of amygdala (CeAGABA), activation of which could block methamphetamine (METH)-primed conditioned place preference (CPP) in mice.

An orexigenic role for μ-opioid receptors in the lateral parabrachial nucleus

2003 ◽  
Vol 285 (5) ◽  
pp. R1055-R1065 ◽  
Author(s):  
John D. Wilson ◽  
Danielle M. Nicklous ◽  
Vincent J. Aloyo ◽  
Kenny J. Simansky
Keyword(s):  
Food Intake ◽  
Male Rats ◽  
Parabrachial Nucleus ◽  
Opioid Antagonist ◽  
Free Access ◽  
Lateral Parabrachial Nucleus ◽  
Μ Opioid Receptor ◽  
Access To Food ◽  
The Brain ◽  
Μ Opioid Receptors

The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective μ-opioid receptor (μ-OR) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 μl) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective μ-opioid antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the κ-antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating μ-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate μ-ORs in the LPBN in the normal regulation of food intake.

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