Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

Huang, Hao; Xu, Youfen; van den Pol, Anthony N.

doi:10.1152/jn.00740.2010

Cited by 70Regulation of Appetite and ObesityNicotinic Acetylcholine Receptors StudySmoking Behavior and Cessation

Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

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Huang, Hao, Xu, Youfen, van den Pol, Anthony N.·2011·Journal of Neurophysiology

DOI 10.1152/jn.00740.2010PMC PMC3174824

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Abstract

Two of the biggest health problems facing us today are addiction to nicotine and the increased prevalence of obesity. Interestingly, nicotine attenuates obesity, but the underlying mechanism is not clear. Here we address the hypothesis that if weight-reducing actions of nicotine are mediated by anorexigenic proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus, nicotine should excite these cells. Nicotine at concentrations similar to those found in smokers, 100-1,000 nM, excited POMC cells by mechanisms based on increased spike frequency, depolarization of membrane potential, and opening of ion channels. This was mediated by activation of both α7 and α4β2 nicotinic receptors; by itself, this nicotine-mediated excitation could explain weight loss caused by nicotine. However, in control experiments nicotine also excited the orexigenic arcuate nucleus neuropeptide Y (NPY) cells. Nicotine exerted similar actions on POMC and NPY cells, with a slightly greater depolarizing action on POMC cells. Immunocytochemistry revealed cholinergic axons terminating on both cell types. Nicotine actions were direct in both cell types, with nicotine depolarizing the membrane potentials and reducing input resistance. We found no differences in the relative desensitization to nicotine between POMC and NPY neurons. Nicotine inhibited excitatory synaptic activity recorded in NPY, but not POMC, cells. Nicotine also excited hypocretin/orexin neurons that enhance cognitive arousal, but the responses were smaller than in NPY or POMC cells. Together, these results indicate that nicotine has a number of similar actions, but also a few different actions, on POMC and NPY neurons that could contribute to the weight loss associated with smoking.

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In the arcuate nucleus of the hypothalamus, nicotine increases the firing rate of both POMC- and NPY-positive neurons.
“In the arcuate nucleus of the hypothalamus, nicotine increases the firing rate of both POMC- and neuropeptide Y (NPY)-positive neurons”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Huang et al., 2011
The increase in POMC neuron activity predominates in vitro due to more rapid desensitization of nAChR responses in NPY neurons.
“although the increase in POMC neuron activity predominates in vitro due to more rapid desensitization of nAChR responses in NPY neurons”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Huang et al., 2011
In vivo, nicotine increases c-fos immunoreactivity predominantly in POMC-positive cells.
“and in vivo, as evidenced by an increase in c-fos immunoreactivity predominantly in POMC-positive cells (Huang et al., 2011; Mineur et al., 2011).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Huang et al., 2011

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Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats
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The Activation of Nicotinic Acetylcholine Receptors Enhances the Inhibitory Synaptic Transmission in the Deep Dorsal Horn Neurons of the Adult Rat Spinal Cord
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Voluntary ethanol consumption in the absence of hunger and thirst drives
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Sorted by citations

Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.036 · Cited by 1,404 · see citing works
The endocrine effects of nicotine and cigarette smoke
Tweed, J. O., Hsia, S. H., Lutfy, K., & Friedman, T. C. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.03.006 · Cited by 231 · see citing works
“Recent studies in rodents have shown that nicotine suppresses appetite ultimately via the activation of melanocortin-4 receptors (MC4R) expressed on hypothalamic pro-opiomelanocortin (POMC) neurons [55,56] that signals satiety.”
Background
Molecular Mechanisms Underlying Behaviors Related to Nicotine AddictionPreprint
Picciotto, M. R., & Kenny, P. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012112 · Cited by 178 · see citing works
“There are a number of nAChR subtypes expressed in the hypothalamus (Jo et al. 2002, 2005), and nicotine can stimulate the firing of both POMC neurons, which signal satiety, and neuropeptide Y (NPY) neurons, which stimulate food seeking (Huang et al. 2011).”
POMC Neurons: From Birth to Death
Toda, C., Santoro, A. N., Kim, J. D., & Diano, S. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034110 · Cited by 165 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
“Acute nicotine administration excited orexin-expressing neurons in the lateral hypothalamus/perifornical area (Huang et al., 2011) and dose dependently increased Fos expression in these brain regions (Pasumarthi et al., 2006).”
Background
Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits
Alhadeff, A. L., Goldstein, N., Park, O., Klima, M. L., Vargas, A. P.-D., & Betley, J. N. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.050 · Cited by 129 · see citing works
“Similar activity changes at AgRP and POMC neurons, although uncommon, have been previously observed (Huang et al., 2011).”
Anti-inflammatory effects of nicotine in obesity and ulcerative colitis
Lakhan, S. E., & Kirchgessner, A. L. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-129 · Cited by 128 · see citing works
“Nicotine inhibited excitatory synaptic activity recorded in NPY, but not POMC neurons and also excited the arcuate nucleus hypocretin/orexin neurons that enhance cognitive arousal, but the responses were smaller than in POMC neurons [59].”
Background
Molecules and circuits involved in nicotine addiction: The many faces of smoking
Picciotto, M. R., & Mineur, Y. S. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.028 · Cited by 117 · see citing works
“, 2013), likely due to the activation of melanocortin system (Huang et al., 2011; Mineur et al., 2011).”
BackgroundInfluential
Cholinergic neurons in the dorsomedial hypothalamus regulate food intake
Jeong, J. H., Lee, D., & Jo, Y. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.01.001 · Cited by 87 · see citing works
“Activation of nicotinic acetylcholine receptors (nAChRs) reduces food intake via modulation of melanocortinergic neurons in the arcuate nucleus of the hypothalamus (ARC) [1,2].”
BackgroundInfluential
Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease
Candler, T. P., Kühnen, P., Prentice, A. M., & Silver, M. J. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100773 · Cited by 83 · see citing works
Nicotinic Regulation of Energy Homeostasis
Zoli, M., & Picciotto, M. R. (2012) · Nicotine & Tobacco Research · doi:10.1093/ntr/nts159 · Cited by 77 · see citing works
“Nicotine exposure also has a direct excitatory effect on POMC neurons (Huang et al., 2011; Mineur et al., 2011), slightly stronger than that observed for NPY neurons (Huang et al.”
BackgroundInfluential
Effects of nicotine on homeostatic and hedonic components of food intake
Stojakovic, A., Espinosa, E. V. P., Farhad, O. T., & Lutfy, K. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0166 · Cited by 65 · see citing works
Orexin/Hypocretin System: Role in Food and Drug Overconsumption
Barson, J. R., & LEIBOWITZ, S. F. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.06.006 · Cited by 64 · see citing works
Nicotine and energy balance: A review examining the effect of nicotine on hormonal appetite regulation and energy expenditure
Schwartz, A., & Bellissimo, N. (2021) · Appetite · doi:10.1016/j.appet.2021.105260 · Cited by 59 · see citing works
Astragaloside IV Prevents Obesity-Associated Hypertension by Improving Pro-Inflammatory Reaction and Leptin Resistance.
Jiang, P., Ma, D., Wang, X., Wang, Y., Bi, Y., Jl, Y., Wang, X., & Li, X. (2018) · PubMed Central · doi:10.14348/molcells.2018.2156 · Cited by 54 · see citing works
“In the hypothalamic neurons and peripheral adipose tissue, abundant α7nAChR have been found (Huang et al., 2011).”
Background
The role of alpha-7 nicotinic receptors in food intake behaviors
Legget, K. T., Cornier, M., & Tregellas, J. R. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00553 · Cited by 49 · see citing works
“Frontiers in Psychology | Eating Behavior June 2014 | Volume 5 | Article 553 | 2 by nicotine, inhibition of excitatory synaptic activity (glutamate release) on NPY neurons was also observed, an effect not seen in POMC neurons (Huang et al., 2011).”
The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease
Zhu, P., Sun, W., Zhang, C.-L., Song, Z.-Y., & Lin, S. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.06.138 · Cited by 45 · see citing works
Weight loss through smoking
Seeley, R. J., & Sandoval, D. A. (2011) · Nature · doi:10.1038/475176a · Cited by 40 · see citing works
Nicotine’ actions on energy balance: Friend or foe?
Seoane‐Collazo, P., Diéguez, C., Nogueiras, R., Rahmouni, K., Fernández‐Real, J. M., & López, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107693 · Cited by 39 · see citing works
“…nicotine treatment (Kane, Parker, & Li, 2001; Li et al., 2000); ii) the activation of NPY neurons by nicotine may occur to a lesser extentthan POMC neurons and iii) after nicotine'streatmentaninhibition of glutamate release is observed in NPY neurons, but not in POMC neurons (Huang et al., 2011).”
Influential
Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake
Calarco, C. A., & Picciotto, M. R. (2020) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntz010 · Cited by 40 · see citing works
Anti-Obesity Effect of Arq Zeera and Its Main Components Thymol and Cuminaldehyde in High Fat Diet Induced Obese Rats
Haque, M., & Ansari, H. (2018) · Drug Research · doi:10.1055/a-0590-1956 · Cited by 36 · see citing works
“Leptin alters the release of several neuropeptides after binding to its receptors (leptin receptor (LepR), especially neuropeptide Y (NYP) from the hypothalamus and in the hypothalamus leptin inhibits the expression of NPY [46].”
Background
A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis
Crouser, E. D., Smith, R. M., Culver, D. A., et al. (2021) · CHEST Journal · doi:10.1016/j.chest.2021.05.031 · Cited by 36 · see citing works
Pharmacological Effects and Regulatory Mechanisms of Tobacco Smoking Effects on Food Intake and Weight Control
Hu, T., Yang, Z., & Li, M. D. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9800-y · Cited by 34 · see citing works
Rare deleterious germline variants and risk of lung cancer
Liu, Y., Xia, J., McKay, J., Tsavachidis, S., Xiao, X., Spitz, M. R., Cheng, C., Byun, J., Wei, H., Li, Y., et al. (2021) · npj Precision Oncology · doi:10.1038/s41698-021-00146-7 · Cited by 35 · see citing works
Phytochemicals derived from Nicotiana tabacum L. plant contribute to pharmaceutical development
Zhang, W., Pan, X., Fu, J., Cheng, W., Lin, H., Zhang, W., & Huang, Z. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1372456 · Cited by 40 · see citing works
Nicotinic Cholinergic System in the Hypothalamus Modulates the Activity of the Hypothalamic Neuropeptides During the Stress Response
Balkan, B., & Pöğün, Ş. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170720092442 · Cited by 32 · see citing works
“Indeed, electrophysiological studies demonstrated that nicotine excites hypothalamic POMC neurons in mice through activation of α4β2 and α7 nAChRs present on these neurons [164].”
BackgroundInfluential
Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus
Jeong, J. H., Woo, Y. J., Chua, S. C., & Jo, Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162839 · Cited by 31 · see citing works
“Activation of nicotinic acetylcholine receptors reduces energy intake via modulation of melanocortinergic neurons in the ARC [13, 14].”
Background
International Union of Basic and Clinical Pharmacology CXIV: Orexin Receptor Function, Nomenclature and Pharmacology
Kukkonen, J. P., Jacobson, L. H., Hoyer, D., Rinne, M. K., & Borgland, S. L. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.000953 · Cited by 28 · see citing works
Plasma neuropeptide Y levels relate cigarette smoking and smoking cessation to body weight regulation
Hussain, T., Al‐Daghri, N. M., Al-Attas, O. S., Draz, H. M., Abd-Alrahman, S. H., & Yakout, S. M. (2012) · Regulatory Peptides · doi:10.1016/j.regpep.2012.02.005 · Cited by 27 · see citing works
“For example, nicotine at concentrations similar to those found in cigarette smoke is able to excite anorectic POMC neurons in the hypothalamus and reduce the body weight, linking this neuropeptide to weight loss associated with smoking [47].”
Smoking is Associated with Reduced Leptin and Neuropeptide Y Levels and Higher Pain Experience in Patients with Fibromyalgia
Bokarewa, M. I., Erlandsson, M. C., Bjersing, J. L., Dehlin, M., & Mannerkorpi, K. (2014) · Mediators of Inflammation · doi:10.1155/2014/627041 · Cited by 26 · see citing works
“In animal models smoking supports NpY production by direct activation of the a7 and a4b2 nicotinic receptors in the hypothalamus [49] or by regulation of leptin levels in adipose tissue [50].”
Background
Modeling drug exposure in rodents using e-cigarettes and other electronic nicotine delivery systems
Miliano, C., Scott, E. R., Murdaugh, L. B., Gnatowski, E. R., Faunce, C. L., Anderson, M. S., Reyes, M. M., Gregus, A. M., & Buczynski, M. W. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.108458 · Cited by 25 · see citing works
Cholinergic and Adenosinergic Modulation of Synaptic Release
Yang, D., Ding, C., Qi, G., & Feldmeyer, D. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2020.06.006 · Cited by 24 · see citing works
Acetylcholine Acts through Nicotinic Receptors to Enhance the Firing Rate of a Subset of Hypocretin Neurons in the Mouse Hypothalamus through Distinct Presynaptic and Postsynaptic Mechanisms
Zhou, W., Gao, X., & Picciotto, M. R. (2015) · eNeuro · doi:10.1523/eneuro.0052-14.2015 · Cited by 24 · see citing works
“In our experimental paradigm, either pressure application of ACh (1 mM) onto the soma and the proximal processes or bath application of nicotine (1 μM) suppressed the spontaneous mEPSC frequency in Hcrt+ neurons, which is consistent with effects reported in the arcuate nucleus of the hypothalamus (Huang et al., 2011).”
BackgroundMethod
Not all smokers appear to seek nicotine for the same reasons: implications for preclinical research in nicotine dependence
Garcia‐Rivas, V., & Deroche‐Gamonet, V. (2018) · Addiction Biology · doi:10.1111/adb.12607 · Cited by 25 · see citing works
Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus
Calarco, C. A., Li, Z., Taylor, S. R., Lee, S., Zhou, W., Friedman, J. M., Mineur, Y. S., Gotti, C., & Picciotto, M. R. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13966 · Cited by 24 · see citing works
“Nicotine alters the electrophysiological excitability (Huang et al., 2011; Mineur et al., 2011), and neuropeptide expression levels (Calarco, Lee, & Picciotto, 2017; Chen, Saad, Sandow, & Bertrand, 2012; Fornari et al., 2007; Frankish et al., 1995; Hur, Hong, Choi, Shin, & Chun, 2010) in both AgRP…”
BackgroundInfluential
Multidimensional Intersection of Nicotine, Gene Expression, and Behavior
Sherafat, Y., Bautista, M. R., & Fowler, C. D. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.649129 · Cited by 22 · see citing works
Nicotinic Cholinergic Signaling in Adipose Tissue and Pancreatic Islets Biology: Revisited Function and Therapeutic Perspectives
Somm, E. (2013) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-013-0266-6 · Cited by 24 · see citing works
Hypothalamic proteome changes in response to nicotine and its withdrawal are potentially associated with alteration in body weight
Gao, M., Hu, F., Zeng, X.-D., Tang, H.-L., Zhang, H., Jiang, W., Yan, H.-J., Shi, H., Shu, Y., & Long, Y. (2020) · Journal of Proteomics · doi:10.1016/j.jprot.2020.103633 · Cited by 18 · see citing works
Nicotine, Food Intake, and Activation of POMC Neurons
Picciotto, M. R., & Mineur, Y. S. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.163 · Cited by 17 · see citing works
Nicotinic α4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits
García, A. P., Aitta‐aho, T., Schaaf, L., Heeley, N., Heuschmid, L., Bai, Y., Barrantes, F. J., & Apergis‐Schoute, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133327 · Cited by 18 · see citing works
Overnight Fasting Regulates Inhibitory Tone to Cholinergic Neurons of the Dorsomedial Nucleus of the Hypothalamus
Groessl, F., Jeong, J. H., Talmage, D. A., Role, L. W., & Jo, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060828 · Cited by 15 · see citing works
Hypocretin/Orexin and Plastic Adaptations Associated with Drug Abuse
Baimel, C., & Borgland, S. L. (2016) · Current topics in behavioral neurosciences · doi:10.1007/7854_2016_44 · Cited by 15 · see citing works
Gene expression of pro-opiomelanocortin and melanocortin receptors is regulated in the hypothalamus and mesocorticolimbic system following nicotine administration
Tapınc, D. E., Ilgın, R., Kaya, E., Gözen, O., Ugur, M., Koylu, E. O., Kanıt, L., Keser, A., & Balkan, B. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.11.049 · Cited by 14 · see citing works
Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice
Dezfuli, G., Kellar, K. J., Dretchen, K. L., Tizabi, Y., Sahibzada, N., & Gillis, R. A. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.020 · Cited by 13 · see citing works
Changes in gut-brain axis parameters in adult rats of both sexes with different feeding pattern that were early nicotine-exposed
Rodrigues, V. S. T., de Moura, E. G., Peixoto, T. C., Soares, P. N., Lopes, B. P., Oliveira, E., Manhães, A. C., Atella, G. C., Kluck, G. E. G., Cabral, S. S., et al. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112656 · Cited by 11 · see citing works
Alteration of orexin-A and PKCα in the postmortem brain of pure-opioid and multi-drug abusers
Sadat‐Shirazi, M., Soltani, H., Nikpour, N., Haghshenas, M., Khalifeh, S., Mokri, A., & Zarrindast, M. (2020) · Neuropeptides · doi:10.1016/j.npep.2020.102074 · Cited by 11 · see citing works
Orexin-mediated motivated arousal and reward seeking
Bjorness, T. E., & Greene, R. W. (2024) · Peptides · doi:10.1016/j.peptides.2024.171280 · Cited by 10 · see citing works
Magnesium and Zinc Involvement in Tobacco Addiction
Nechifor, M. (2012) · Journal of Addiction Research & Therapy · doi:10.4172/2155-6105.s2-005 · Cited by 10 · see citing works
The effects of noncontingent and self-administered cytisine on body weight and meal patterns in male Sprague–Dawley rats
Grebenstein, P. E., Harp, J. L., & Rowland, N. E. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.07.012 · Cited by 9 · see citing works
“Both α7 and α4β2 receptors have been found throughout the ventromedial hypothalamus (Zoli and Picciotto, 2012) and are important in nicotine-induced depolarization of NPY and POMC neurons (Huang et al., 2011).”
Background
Cocaine and Nicotine Research Illustrates a Range of Hypocretin Mechanisms in Addiction
Baimel, C., Borgland, S. L., & Corrigall, W. A. (2012) · Vitamins and hormones · doi:10.1016/b978-0-12-394623-2.00016-0 · Cited by 8 · see citing works
“Recently, Huang et al. (2011) reported electrophysiological evidence that nicotine could excite hcrt-containing neurons in the LH/PFA; nicotine depolarized hcrt neurons and increased spike frequency, although to a lesser extent than it affected proopiomelanocortin or neuropeptide Y cells of the…”
Background
Food-Induced Increase of Acetylcholine in Mouse Hypothalamus
Thinnes, A., & Klein, J. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00173 · Cited by 8 · see citing works
Cholinergic control of GnRH neuron physiology and luteinizing hormone secretion in male mice: involvement of ACh/GABA co-transmission
Vastagh, C., Farkas, I., Csillag, V., Watanabe, M., Kalló, I., & Liposits, Z. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1780-23.2024 · Cited by 8 · see citing works
“In the hypothalamus, similar nAChR-dependent activation was reported in POMC neurons (Huang et al., 2011).”
Background
Levamisole: A Positive Allosteric Modulator for the α3β4 Nicotinic Acetylcholine Receptors Prevents Weight Gain in the CD-1 Mice on a High Fat Diet
Lewis, J. A., Yakel, J. L., & Pandya, A. A. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666161201145648 · Cited by 7 · see citing works
“While the α7, α4β2 and α3β4 receptors are reported to be present on the POMC neurons [6, 21], results obtained in this study show that PAMs selective for α7 and α4β2 receptors, PNU-120596 and dFBr respectively, failed to prevent weight gain in the CD-1 mice that were fed a diet high in fat content.”
BackgroundResult
In-Operando Quantification of Electrode Flooding in CO 2 Electrolysis and Correlation to Product Distribution
Rottmann, D. M., Kollmuss, R., Haufe, S., et al. (2025) · Journal of The Electrochemical Society · doi:10.1149/1945-7111/add569 · Cited by 5 · see citing works
α4β2 nicotinic acetylcholine receptors intrinsically influence body weight in mice
Dezfuli, G., Olson, T. T., Martin, L. M., Keum, Y., Siegars, B., Desai, A., Uitz, M., Sahibzada, N., Gillis, R. A., & Kellar, K. J. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107921 · Cited by 5 · see citing works
Microstructural meal pattern analysis reveals a paradoxical acute increase in food intake after nicotine despite its long-term anorexigenic effects
Shankar, K., Ambroggi, F., & George, O. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06071-2 · Cited by 4 · see citing works
Acute nicotine activates orectic and inhibits anorectic brain regions in rats exposed to chronic nicotine
Shankar, K., Bonnet-Zahedi, S., Milan, K. K., D'argence, A. R., Sneddon, E. A., Qiao, R., Chonwattangul, S., Carrette, L. L. G., Kallupi, M., & George, O. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.109959 · Cited by 3 · see citing works
“However, nicotine also activates AgRP neurons (Huang et al., 2011), so it is unclear whether this signaling may contribute to the short-term increase in feeding we observed (Shankar et al., 2022).”
Genistein improve nicotine toxicity on male mice pancreas
Salahshoor, M. R., Mirzaei, F., Roshankhah, S., et al. (2019) · Anatomy & Cell Biology · doi:10.5115/acb.2019.52.2.183 · Cited by 3 · see citing works
Availability of Central α4β2* Nicotinic Acetylcholine Receptors in Human Obesity
de Palma, E. S., Günnewig, T., Rullmann, M., Luthardt, J., Hankir, M. K., Meyer, P., Becker, G., Patt, M., Martin, S., Hilbert, A., et al. (2022) · Brain Sciences · doi:10.3390/brainsci12121648 · Cited by 4 · see citing works
“Moreover, nicotinic agonists decrease food intake, body mass index (BMI, kg/m2), and weight gain by activating the hypothalamic pro-opiomelanocortin (POMC) neuron pathway through the central activation of α3β4* nAChR [13,14].”
Background
Cocaine- and amphetamine-regulated transcript promoter regulated by nicotine in nerve growth factor-treated PC12 cells
Ugur, M., Kanıt, L., Koylu, E. O., Balkan, B., & Gözen, O. (2019) · Physiology International · doi:10.1556/2060.106.2019.27 · Cited by 2 · see citing works
“In addition, CART is highly coexpressed with proopiomelanocortin in hypothalamic neurons (19), which are suggested to contain α4β2 and α7 nAChRs (22, 39).”
Background
Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons
Ramírez-Sánchez, E., Mondragón-García, A., Garduño, J., Hernández-Vázquez, F., Ortega-Tinoco, S., & Hernández‐López, S. (2024) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2024.102682 · Cited by 2 · see citing works
“Huang et al. (2011) showed that nicotine increased the firing rate of POMC and NPY neurons.”
Background
Cholinergic control of GnRH neuron physiology and luteinizing hormone secretion: involvement of ACh/GABA co-transmissionPreprint
Vastagh, C., Farkas, I., Csillag, V., Watanabe, M., Kalló, I., & Liposits, Z. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.22.554236 · Cited by 1 · see citing works
FATORES ASSOCIADOS À PERDA DO EXCESSO DE PESO EM OBESOS MÓRBIDOS SUBMETIDOS AO BY-PASS GÁSTRICO EM "Y DE ROUX" AO LONGO DE SESSENTA MESES
Barhouch, A. S. (2015) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Experimental Studies of Subdiaphragmatic Vagotomy and Nicotine for Reducing Body Weight
Dezfuli, G. (2014) · DigitalGeorgetown (Georgetown University Library)
Tobacco Smoking, Food Intake, and Weight Control
Li, M. D. (2018) · Springer eBooks · doi:10.1007/978-981-10-7530-8_15
Effects of Chronic Electronic Vapor Exposure on Body Weight, Appetite, and Metabolism
Breit, M. J. (2017) · doi:10.33915/etd.5257
“…see any significant differences, nicotine has been shown to excite both hypothalamic NPY and POMC neurons through binding to α7nAChRs on the neurons (Huang et al. 2011), with a greater depolarization and spike frequency response from POMC neurons, eliciting a potential mechanism through which…”
BackgroundInfluential
[Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice].
Bao, H., Wang, S., Lu, M., Wang, Y., Jiang, P., & Li, X. (2024) · PubMed Central · doi:10.12122/j.issn.1673-4254.2024.03.11
Activation of α7 nicotinic receptors attenuated hyperalgesia and anxiety induced by palatable obesogenic diet withdrawal.
Alsharari, S. D., Alameen, A. A., Aldafiri, F. S., Ali, Y. S., Alshammari, M. A., Sari, Y., & Damaj, M. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.07.006
Regulation of Melanogenesis in Skin Epidermal Keratinocytes via Activation of α7 Nicotinic Acetylcholine Receptor on the Expression of α‐Melanocyte‐Stimulating Hormone
Guo, M. S., Wang, X., Xia, Y., Wu, J., Dilidaer, A., Gao, J., Dong, T. T.-X., & Tsim, K. W. K. (2025) · The FASEB Journal · doi:10.1096/fj.202502535r · Cited by 1 · see citing works
Regulation of Neuronal Nicotinic Receptor Expression by Novel Ligands and Mechanisms
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Authors: Huang, H., Xu, Y., & van den Pol, A. N.
Affiliations: Yale University (US)
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
ORCID: Huang, Hao
Venue: Journal of Neurophysiology
Publisher: American Physiological Society
Published: 2011-09
Volume: 106
Issue: 3
Pages: 1191-1202
ISSN: 0022-3077 (ISSN-L)
1522-1598
DOI: 10.1152/jn.00740.2010
PMC: PMC3174824
OpenAlex: W2132107197
Semantic Scholar: 1e1847a2f4e5c1e74d661bd58192540d807b11b3
Cited by: 70
References: 87
Citations by year: 2025: 2 · 2024: 8 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 9
FWCI: 2.66
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Neurophysiology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS048476, NS 41454, R01NS041454, NS48476)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords: nicotine, proopiomelanocortin neurons, neuropeptide Y neurons, arcuate nucleus, hypothalamus, nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, alpha4beta2 nicotinic receptor, membrane depolarization, input resistance, synaptic inhibition, hypocretin/orexin neurons, weight loss, obesity, smoking, cholinergic axons
MeSH terms: Orexins, Action Potentials, Animals, Appetite Depressants, Arcuate Nucleus of Hypothalamus, Mice, Transgenic, Neurons, Neuropeptide Y, Neuropeptides, Nicotine, Pro-Opiomelanocortin, Intracellular Signaling Peptides and Proteins, Mice

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Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

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