Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN
Open accessAbstract
Neuropepetide Y (NPY) is best known for its powerful stimulation of food intake and its effects on reducing energy expenditure. However, the pathways involved and the regulatory mechanisms behind this are not well understood. Here we demonstrate that NPY derived from the arcuate nucleus (Arc) is critical for the control of sympathetic outflow and brown adipose tissue (BAT) function. Mechanistically, a key change induced by Arc NPY signaling is a marked Y1 receptor-mediated reduction in tyrosine hydroxylase (TH) expression in the hypothalamic paraventricular nucleus (PVN), which is also associated with a reduction in TH expression in the locus coeruleus (LC) and other regions in the brainstem. Consistent with this, Arc NPY signaling decreased sympathetically innervated BAT thermogenesis, involving the downregulation of uncoupling protein 1 (UCP1) expression in BAT. Taken together, these data reveal a powerful Arc-NPY-regulated neuronal circuit that controls BAT thermogenesis and sympathetic output via TH neurons.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Obesity is accompanied by an increased NPY expression in the ARC.
“Obesity is also accompanied by an increased NPY expression in the ARC.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [129]
Increased NPY expression triggers a reduction in the expression of tyrosine hydroxylase neurons in the PVN of the hypothalamus and consequently diminishes the thermogenic activation of BAT and overall energy expenditure.
“This increase triggers a reduction in the expression of tyrosine hydroxylase neurons in the paraventricular nucleus (PVN) of the hypothalamus and consequently, diminishes the thermogenic activation of BAT and overall energy expenditure 129.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [129]
Cites
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864 · see citing works
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058 · see citing works
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356 · see citing works
Gut hormone PYY3-36 physiologically inhibits food intake
Batterham, R. L., Cowley, M. A., Small, C. J., Herzog, H., Cohen, M. A., Dakin, C. L., Wren, A. M., Brynes, A. E., Low, M. J., Ghatei, M. A., et al. (2002) · Nature · doi:10.1038/nature00887 · Cited by 2,351 · see citing works
Self-citationAdipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · cited 2× · see citing works
“Obesity occurs when there is a significant imbalance between energy intake and energy expenditure (Rosen and Spiegelman, 2006).”
BackgroundHypothalamic integration: organization of the paraventricular and supraoptic nuclei
Swanson, L. W., & Sawchenko, P. E. (1983) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.06.030183.001413 · Cited by 1,991 · see citing works
Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein
Ollmann, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., & Barsh, G. S. (1997) · Science · doi:10.1126/science.278.5335.135 · Cited by 1,881 · see citing works
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164 · see citing works
Paraventricular Nucleus:A Site for the Integration of Neuroendocrine and Autonomic Mechanisms
Swanson, L. W., & Sawchenko, P. E. (2008) · Neuroendocrinology · doi:10.1159/000123111 · Cited by 1,001 · see citing works
King, B. M. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.10.007 · Cited by 490 · see citing works
Zarjevski, N., Cusin, I., Vettor, R., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404618 · Cited by 476 · see citing works
Localization of insulin receptor mRNA in rat brain by in situ hybridization
MARKS, J. L., PORTE, D., STAHL, W. L., & BASKIN, D. G. (1990) · Endocrinology · doi:10.1210/endo-127-6-3234 · Cited by 448 · see citing works
Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S., & Saper, C. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.741 · Cited by 376 · see citing works
Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H., & Wakabayashi, I. (2000) · Endocrinology · doi:10.1210/endo.141.12.7920 · Cited by 374 · see citing works
NPY and Y receptors: lessons from transgenic and knockout models
Lin, S., Boey, D., & Herzog, H. (2004) · Neuropeptides · doi:10.1016/j.npep.2004.05.005 · Cited by 282 · see citing works
Self-citationParaventricular hypothalamic nucleus: Axonal projections to the brainstem
Geerling, J. C., Shin, J., Chimenti, P. C., & Loewy, A. D. (2010) · Journal of Comparative Neurology · doi:10.1002/cne.22283 · Cited by 273 · see citing works
Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats
Egawa, M., Yoshimatsu, H., & Bray, G. A. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.2.r328 · Cited by 272 · see citing works
Ellacott, K. L. J. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.395 · Cited by 262 · see citing works
Sainsbury, A., Schwarzer, C., Couzens, M., Fetissov, S. O., Fürtinger, S., Jenkins, A. B., Cox, H. M., Sperk, G., Hökfelt, T. G. M., & Herzog, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132043299 · Cited by 246 · see citing works
Self-citationChao, P.-T., Yang, L., Aja, S. M., Moran, T. H., & Bi, S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.02.019 · Cited by 206 · see citing works
Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain
Lin, S., Storlien, L. H., & Huang, X. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02580-4 · Cited by 194 · see citing works
Self-citationHypothalamic projections to locus coeruleus neurons in rat brain
Reyes, B. A. S., Valentino, R. J., Xu, G., & Bockstaele, E. J. V. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04197.x · Cited by 172 · see citing works
Clinical significance of adaptive thermogenesis
Major, G., Doucet, É., Trayhurn, P., Astrup, A. V., & Tremblay, A. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803523 · Cited by 170 · see citing works
The MONA LISA hypothesis in the time of leptin.
Bray, G. A., & York, D. A. (1998) · PubMed · Cited by 166 · see citing works
Role of Dorsomedial Hypothalamic Neuropeptide Y in Modulating Food Intake and Energy Balance
Yang, L., Scott, K. A., Hyun, J., Tamashiro, K. L., Tray, N., Moran, T. H., & Bi, S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4379-08.2009 · Cited by 159 · see citing works
Neuropeptide Y is neuroproliferative for post‐natal hippocampal precursor cells
Howell, O. W., Scharfman, H. E., Herzog, H., Sundström, L., Beck‐Sickinger, A. G., & Gray, W. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01895.x · Cited by 158 · see citing works
Self-citationRole of ventromedial hypothalamus on sympathetic efferents of brown adipose tissue
Niijima, A., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.247.4.r650 · Cited by 150 · see citing works
Using brown adipose tissue to treat obesity – the central issue
Whittle, A. J., López, M., & Vidal‐Puig, A. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.04.001 · Cited by 137 · see citing works
Behavioural profile of a new mouse model for NPY deficiency
Karl, T., Duffy, L., & Herzog, H. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06306.x · Cited by 127 · see citing works
Self-citationRole of melanocortins in the central control of feeding
Vergoni, A. V., & Bertolini, A. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00538-0 · Cited by 125 · see citing works
Sainsbury, A., Rohner-Jeanrenaud, F., Cusin, I., Zakrzewska, K. E., Halban, P. A., Gaillard, R. C., & Jeanrenaud, B. (1997) · Diabetologia · doi:10.1007/s001250050820 · Cited by 115 · see citing works
Self-citationFunctions for pro-opiomelanocortin-derived peptides in obesity and diabetes
Mountjoy, K. G. (2010) · Biochemical Journal · doi:10.1042/bj20091957 · Cited by 108 · see citing works
Role of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit
Sainsbury, A., & Zhang, L. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.09.025 · Cited by 108 · see citing works
Self-citationNguyen, A., Mitchell, N. F., Lin, S., Macia, L., Yulyaningsih, E., Baldock, P. A. J., Enriquez, R. F., Zhang, L., Shi, Y., Zolotukhin, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040191 · Cited by 104 · see citing works
Self-citationSainsbury, A., Cusin, I., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1997) · Diabetes · doi:10.2337/diab.46.2.209 · Cited by 103 · see citing works
Self-citationTolle, V., & Low, M. J. (2007) · Diabetes · doi:10.2337/db07-0733 · Cited by 100 · see citing works
Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion
Zhang, L., Macia, L., Turner, N. A., Enriquez, R. F., Riepler, S. J., Nguyen, A., Lin, S., Lee, N. J., Shi, Y. C., Yulyaningsih, E., et al. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.232 · Cited by 68 · see citing works
Self-citationBrown fat and obesity: the next big thing?
Stephens, M., Ludgate, M. E., & Rees, A. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04018.x · Cited by 65 · see citing works
ZHENG, J.-Q., Seki, M., Hayakawa, T., Ito, H., & Zyo, K. (1995) · Okajimas Folia Anatomica Japonica · doi:10.2535/ofaj1936.72.2-3_119 · Cited by 60 · see citing works
Peripheral‐Specific Y2 Receptor Knockdown Protects Mice From High‐Fat Diet‐Induced Obesity
Shi, Y., Lin, S., Castillo, L. E., Aljanova, A., Enriquez, R. F., Nguyen, A., Baldock, P. A. J., Zhang, L., Bijker, M. S., Macia, L., et al. (2011) · Obesity · doi:10.1038/oby.2011.99 · Cited by 60 · see citing works
Self-citationHorváth, T. L., Naftolin, F. N., & Leranth, C. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90323-t · Cited by 58 · see citing works
Lin, E.-J. D., Sainsbury, A., Lee, N. J., Boey, D., Couzens, M., Enriquez, R. F., Slack, K., Bland, R. J., During, M. J., & Herzog, H. (2006) · Endocrinology · doi:10.1210/en.2006-0097 · Cited by 51 · see citing works
Self-citationKawabe, T., Kawabe, K., & Sapru, H. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045180 · Cited by 43 · see citing works
Regulation of α‐Melanocyte‐Stimulating Hormone Release from Hypothalamic Neuronsa
Jégou, S., Blasquez, C., Delbende, C., Bunel, D. T., & Vaudry, H. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb19689.x · Cited by 40 · see citing works
Lundberg, J. M., Rudehill, A., & Sollevi, A. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90401-9 · Cited by 40 · see citing works
Milewicz, A., Mikulski, E., & Bidzinska, B. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801310 · Cited by 34 · see citing works
Lever, J. D., Mukherjee, S., Norman, D., Symons, D., & Jung, R. T. (1988) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(88)90003-3 · Cited by 34 · see citing works
Engel, B. T., Sato, A., & Sato, Y. (1992) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.42.549 · Cited by 17 · see citing works
Baranowska, B., Wolińska‐Witort, E., Martyńska, L., Chmielowska, M., Mazurczak-Pluta, T., Boguradzka, A., & Baranowska-Bik, A. (2005) · PubMed · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Obesity-associated variants within FTO form long-range functional connections with IRX3
Smemo, S., Tena, J. J., Kim, K.-H., Gamazon, E. R., Sakabe, N. J., Gómez-Marín, C., Aneas, I., Credidio, F. L., Sobreira, D. R., Wasserman, N. F., et al. (2014) · Nature · doi:10.1038/nature13138 · Cited by 1,219 · see citing works
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Timper, K., & Brüning, J. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026609 · Cited by 802 · see citing works
Adipose tissue in control of metabolism
Luo, L., & Liu, M. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0211 · Cited by 707 · see citing works
Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson, M. J., & Horváth, T. L. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.026 · Cited by 439 · see citing works
Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure
Morrison, S. F., Madden, C. J., & Tupone, D. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.007 · Cited by 427 · see citing works
Breton, J., Tennoune, N., Lucas, N., Francois, M., Legrand, R., Jacquemot, J., Goichon, A., Guérin, C., Peltier, J., Pestel-Caron, M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.017 · Cited by 321 · see citing works
Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance.
Schneeberger, M., Gomis, R., & Claret, M. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0398 · Cited by 301 · see citing works
Regulation of energy homeostasis by the NPY system
Loh, K., Herzog, H., & Shi, Y.-C. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.01.003 · Cited by 293 · see citing works
Self-citationO-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan, H.-B., Dietrich, M. O., Liu, Z.-W., Zimmer, M. R., Li, M.-D., Singh, J. P., Zhang, K., Yin, R., Wu, J., Horvath, T. L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.010 · Cited by 281 · see citing works
Neuronal circuits that regulate feeding behavior and metabolism
Sohn, J., Elmquist, J. K., & Williams, K. W. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.05.003 · Cited by 273 · see citing works
The Temperature Dependence of Sleep
Harding, E. C., Franks, N. P., & Wisden, W. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00336 · Cited by 261 · see citing works
“Arcuate NPY neurons that normally stimulate eating also downregulate BAT thermogenesis and so may have similar roles in thermoregulatory connections to sleep (Shi et al., 2013).”
BackgroundNeuronal control of peripheral insulin sensitivity and glucose metabolism
Ruud, J., Steculorum, S. M., & Brüning, J. C. (2017) · Nature Communications · doi:10.1038/ncomms15259 · Cited by 245 · see citing works
Hypothalamic control of energy expenditure and thermogenesis
Tran, L. T., Park, S., Kim, S. K., Lee, J. S., Kim, K. W., & Kwon, O. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00741-z · Cited by 208 · see citing works
Hypothalamic-autonomic control of energy homeostasis
Seoane‐Collazo, P., Fernø, J., González, F., Diéguez, C., Leis, R., Nogueiras, R., & López, M. (2015) · Endocrine · doi:10.1007/s12020-015-0658-y · Cited by 188 · see citing works
Inter‐organ communication: a gatekeeper for metabolic health
Castillo‐Armengol, J., Fajas, L., & Lopez‐Mejia, I. C. (2019) · The EMBO Reports · doi:10.15252/embr.201947903 · Cited by 178 · see citing works
Insulin controls food intake and energy balance via NPY neurons
Loh, K., Zhang, L., Brandon, A. E., Wang, Q., Begg, D. P., Qi, Y., Fu, M., Kulkarni, R. N., Teo, J. D., Baldock, P. A. J., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.013 · Cited by 173 · see citing works
Self-citationRole of leptin in energy expenditure: the hypothalamic perspective
Pandit, R., Beerens, S., & Adan, R. A. H. (2017) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00045.2016 · Cited by 170 · see citing works
Brain regulation of energy balance and body weight
Rui, L. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9261-9 · Cited by 168 · see citing works
Contreras, C., González, F., Fernø, J., Diéguez, C., Rahmouni, K., Nogueiras, R., & López, M. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.919727 · Cited by 163 · see citing works
Obesity: A Review of Pathophysiology and Classification
Busebee, B. T., Ghusn, W., Cifuentes, L., & Acosta, A. J. (2023) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2023.05.026 · Cited by 182 · see citing works
Brown and Beige Adipose Tissues in Health and Disease
Rui, L. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170001 · Cited by 178 · see citing works
The hypothalamic arcuate nucleus and the control of peripheral substrates
Joly‐Amado, A., Cansell, C., Denis, R., Delbès, A.-S., Castel, J., Martinez, S., & Luquet, S. H. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.03.003 · Cited by 147 · see citing works
Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism
Zhang, W., Cline, M. A., & Gilbert, E. R. (2014) · Nutrition & Metabolism · doi:10.1186/1743-7075-11-27 · Cited by 141 · see citing works
Bal, N. C., Singh, S. K., Reis, F. C. G., Maurya, S. K., Pani, S., Rowland, L. A., & Periasamy, M. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.790451 · Cited by 140 · see citing works
Geerling, J. J., Boon, M. R., Kooijman, S., Parlevliet, E. T., Havekes, L. M., Romijn, J. A., Meurs, I. M., & Rensen, P. C. N. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r045013 · Cited by 137 · see citing works
Central Nervous System Regulation of Brown Adipose Tissue
Morrison, S. F., & Madden, C. J. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140013 · Cited by 151 · see citing works
Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect
Chen, W.-C., Liu, Y., Liu, W.-F., Zhou, Y., He, H., & Lin, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580378 · Cited by 136 · see citing works
Self-citationEstrogen-sensitive medial preoptic area neurons coordinate torpor in mice
Zhang, Z., Reis, F. M., He, Y., Park, J. W., DiVittorio, J. R., Sivakumar, N., van Veen, J. E., Maesta‐Pereira, S., Shum, M., Nichols, I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20050-1 · Cited by 138 · see citing works
Dodd, G. T., Worth, A. A., Nunn, N., Korpal, A. K., Bechtold, D. A., Allison, M. B., Myers, M. G., Statnick, M. A., & Luckman, S. M. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.022 · Cited by 127 · see citing works
Martínez-Sánchez, N., Sweeney, O., Sidarta-Oliveira, D., Caron, A., Stanley, S., & Domingos, A. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.017 · Cited by 105 · see citing works
Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions
Ip, C. K., Zhang, L., Farzi, A., Qi, Y., Clarke, I. M., Reed, F. M., Shi, Y., Enriquez, R. F., Dayas, C. V., Graham, B. A., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.04.001 · Cited by 112 · see citing works
Self-citationRole of hypothalamus in aging and its underlying cellular mechanisms
Kim, K., & Choe, H. K. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.04.008 · Cited by 113 · see citing works
Glutamate Mediates the Function of Melanocortin Receptor 4 on Sim1 Neurons in Body Weight Regulation
Xu, Y., Wu, Z., Sun, H., Zhu, Y., Kim, E. R., Lowell, B. B., Arenkiel, B. R., Xu, Y., & Tong, Q. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.003 · Cited by 105 · see citing works
Hypothalamus and thermogenesis: Heating the BAT, browning the WAT
Contreras, C., Nogueiras, R., Diéguez, C., Medina‐Gómez, G., & López, M. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.08.002 · Cited by 102 · see citing works
Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway
Contreras, C., Nogueiras, R., Diéguez, C., Rahmouni, K., & López, M. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.019 · Cited by 100 · see citing works
NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons
Engström, L., Pereira, M. M. A., Solís, A. J. D., Fenselau, H., & Brüning, J. C. (2020) · Nature Communications · doi:10.1038/s41467-020-14291-3 · Cited by 99 · see citing works
Loss of dorsomedial hypothalamic GLP-1 signaling reduces BAT thermogenesis and increases adiposity
Lee, S. J., Sanchez-Watts, G., Krieger, J.-P., Pignalosa, A., Norell, P. N., Cortella, A., Pettersen, K. G., Vrdoljak, D., Hayes, M. R., Kanoski, S. E., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.03.008 · Cited by 95 · see citing works
Xu, Y., Lu, Y., Cassidy, R. M., Mangieri, L. R., Zhu, C., Xugen, H., Jiang, Z., Justice, N. J., Xu, Y., Arenkiel, B. R., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11399-z · Cited by 96 · see citing works
Interactions between central nervous system and peripheral metabolic organs
Zeng, W., Yang, F., Shen, W. L., Zhan, C., Zheng, P., & Hu, J. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2103-5 · Cited by 96 · see citing works
Liu, W., Chen, W., Xie, M., Chen, C., Shao, Z., Zhang, Y., Zhao, H., Song, Q., Hu, H., Xing, X., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01457-w · Cited by 85 · see citing works
Antipsychotics and glucose metabolism: how brain and body collide
Kowalchuk, C., Castellani, L. N., Chintoh, A., Remington, G., Giacca, A., & Hahn, M. K. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00164.2018 · Cited by 85 · see citing works
Cheng, L., Yu, Y., Szabo, A., Wu, Y., Wang, H., Camer, D., & Huang, X. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2014.12.011 · Cited by 80 · see citing works
Self-citationCavin, J., Voitellier, É., Cluzeaud, F., Kapel, N., Marmuse, J., Chevallier, J., Msika, S., Bado, A., & Gall, M. L. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00197.2016 · Cited by 78 · see citing works
Güemes, A., & Georgiou, P. (2018) · Bioelectronic Medicine · doi:10.1186/s42234-018-0009-4 · Cited by 74 · see citing works
Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity
Lee, J. H., Lin, L., Xu, P., Saito, K., Wei, Q., Meadows, A. G., Bongmba, O. Y. N., Pradhan, G., Zheng, H., Xu, Y., et al. (2016) · Diabetes · doi:10.2337/db15-1587 · Cited by 73 · see citing works
Preclinical models for obesity research
Barrett, P., Mercer, J. G., & Morgan, P. J. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.026443 · Cited by 73 · see citing works
Mitochondrial Proteolipid Complexes of Creatine Kinase
Schlattner, U., Kay, L., & Tokarska-Schlattner, M. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-10-7757-9_13 · Cited by 69 · see citing works
Treatment of Acquired Hypothalamic Obesity: Now and the Future
Dimitri, P. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.846880 · Cited by 67 · see citing works
Hypothalamic Regulation of Brown Adipose Tissue Thermogenesis and Energy Homeostasis
Zhang, W., & Bi, S. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00136 · Cited by 67 · see citing works
Diet-induced adaptive thermogenesis requires neuropeptide FF receptor-2 signalling
Zhang, L., Ip, C. K., Lee, I.-C. J., Qi, Y., Reed, F. M., Karl, T., Low, J. K., Enriquez, R. F., Lee, N. J., Baldock, P. A. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06462-0 · Cited by 66 · see citing works
Self-citationNeuropeptides at the crossroad of fear and hunger: a special focus on neuropeptide Y
Comeras, L. B., Herzog, H., & Tasan, R. O. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14179 · Cited by 63 · see citing works
Self-citationNeuronal Control of Brown Fat Activity
Kooijman, S., van den Heuvel, J. K., & Rensen, P. C. N. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.008 · Cited by 64 · see citing works
The new era of drug therapy for obesity: the evidence and the expectations
Jones, B. J., & Bloom, S. R. (2015) · Drugs · doi:10.1007/s40265-015-0410-1 · Cited by 58 · see citing works
Kuperman, Y., Weiss, M., Dine, J., Staikin, K., Golani, O., Ramot, A., Nahum, T., Kühne, C., Shemesh, Y., Wurst, W., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.017 · Cited by 60 · see citing works
Clarke, I. J. (2014) · Hormones and Behavior · doi:10.1016/j.yhbeh.2014.02.005 · Cited by 58 · see citing works
Burke, L. K., Darwish, T., Cavanaugh, A. R., Virtue, S., Roth, E., Morro, J., Liu, S.-M., Xia, J., Dalley, J. W., Burling, K., et al. (2017) · eLife · doi:10.7554/elife.22848 · Cited by 57 · see citing works
Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
Wu, C., Bongmba, O. Y. N., Yue, J., Lee, J., Lin, L., Saito, K., Pradhan, G., Li, D., Pan, H., Xu, A. W., et al. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040832 · Cited by 60 · see citing works
Yan, C., Zeng, T., Lee, K., Nobis, M., Loh, K., Gou, L., Xia, Z., Gao, Z., Bensellam, M., Hughes, W. E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22925-3 · Cited by 60 · see citing works
Self-citationThe regulation of food intake by insulin in the central nervous system
Mitchell, C. S., & Begg, D. P. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12952 · Cited by 60 · see citing works
Huang, Y., Lin, X., & Lin, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.695623 · Cited by 58 · see citing works
Self-citationA novel thermoregulatory role for PDE10A in mouse and human adipocytes
Hankir, M. K., Kranz, M., Gnad, T., Weiner, J., Wagner, S., Deuther‐Conrad, W., Bronisch, F., Steinhoff, K. G., Luthardt, J., Klöting, N., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201506085 · Cited by 58 · see citing works
Seoane‐Collazo, P., Martínez‐Sánchez, N., Milbank, E., & Contreras, C. (2020) · Nutrients · doi:10.3390/nu12020472 · Cited by 58 · see citing works
Olanzapine reduced brown adipose tissue thermogenesis and locomotor activity in female rats
Zhang, Q., Lian, J., He, M., Deng, C., Wang, H., & Huang, X. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.02.003 · Cited by 57 · see citing works
Self-citationCholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism
Jeong, J. H., Lee, D., Blouet, C., Ruiz, H. H., Buettner, C., Chua, S. C., Schwartz, G. J., & Jo, Y. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.006 · Cited by 56 · see citing works
Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways
Shi, Z., Madden, C. J., & Brooks, V. L. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92008 · Cited by 55 · see citing works
Neural Control of Energy Expenditure
Münzberg, H., Qualls‐Creekmore, E., Berthoud, H., Morrison, C. D., & Yu, S. (2015) · Handbook of experimental pharmacology · doi:10.1007/164_2015_33 · Cited by 53 · see citing works
Lau, J., Farzi, A., Qi, Y., Heilbronn, R., Mietzsch, M., Shi, Y., & Herzog, H. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.10.015 · Cited by 55 · see citing works
Self-citationArima, Y., Ohki, T., Nishikawa, N., Higuchi, K., Ota, M., Tanaka, Y., Nio‐Kobayashi, J., Elfeky, M., Sakai, R., Mori, Y., et al. (2017) · eLife · doi:10.7554/elife.25517 · Cited by 53 · see citing works
The role of dietary salt in metabolism and energy balance: Insights beyond cardiovascular disease
Wu, Q., Burley, G., Li, L., Lin, S., & Shi, Y. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14980 · Cited by 57 · see citing works
Self-citationHypothalamic endoplasmic reticulum stress as a key mediator of obesity‐induced leptin resistance
Ye, Z., Liu, G., Guo, J., & Su, Z. (2018) · Obesity Reviews · doi:10.1111/obr.12673 · Cited by 54 · see citing works
Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice
Seimon, R. V., Shi, Y., Slack, K., Lee, K., Fernando, H. A., Nguyen, A., Zhang, L., Lin, S., Enriquez, R. F., Lau, J., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0145157 · Cited by 51 · see citing works
Self-citationDnmt3a in Sim1 Neurons Is Necessary for Normal Energy Homeostasis
Kohno, D., Lee, S., Harper, M. J., Kim, K. W., Sone, H., Sasaki, T., Kitamura, T., Fan, G., & Elmquist, J. K. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1316-14.2014 · Cited by 50 · see citing works
Silva‐Cutini, M. A., de Almeida, S. A., do Nascimento, A. M., Abreu, G. R., Bissoli, N. S., Lenz, D., Endringer, D. C., Brasil, G. A., de Lima, E. M., Biancardi, V. C., et al. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.01.006 · Cited by 50 · see citing works
Gao, F., Hu, Q., Chen, W., Li, J., Qi, C., Yan, Y., Qian, C., Wan, M., Ficke, J. R., Zheng, J., et al. (2024) · Bone Research · doi:10.1038/s41413-024-00316-w · Cited by 49 · see citing works
Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY
Lv, X., Gao, F., Li, T. P., Xue, P., Wang, X., Wan, M., Hu, B., Chen, H., Jain, A., Shao, Z., et al. (2021) · eLife · doi:10.7554/elife.70324 · Cited by 45 · see citing works
Stress- and diet-induced fat gain is controlled by NPY in catecholaminergic neurons
Zhang, L., Lee, I.-C. J., Enriquez, R. F., Lau, J., Vähätalo, L. H., Baldock, P. A. J., Savontaus, E., & Herzog, H. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.05.001 · Cited by 45 · see citing works
Self-citationNeuronal Control of Adaptive Thermogenesis
Yang, X., & Ruan, H. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00149 · Cited by 44 · see citing works
Iwagaki, N., Ganley, R. P., Dickie, A. C., Polgár, E., Hughes, D. I., del Río, P., Revina, Y., Watanabe, M., Todd, A. J., & Riddell, J. S. (2015) · Pain · doi:10.1097/j.pain.0000000000000407 · Cited by 44 · see citing works
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
Self-citationMelanocortin neurons: Multiple routes to regulation of metabolism
Shen, W.-J., Yao, T. S., Kong, X., Williams, K. W., & Liu, T. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.05.007 · Cited by 41 · see citing works
Polyák, Á., Ferenczi, S., Dénes, Á., Winkler, Z., Kriszt, R., Pintér-Kübler, B., & Kovács, K. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.01.010 · Cited by 40 · see citing works
Hypothalamic control of hepatic lipid metabolism via the autonomic nervous system
Bruinstroop, E., Fliers, E., & Kalsbeek, A. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.05.001 · Cited by 39 · see citing works
Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK
Liu, M., Alimov, A. P., Wang, H., Frank, J. A., Katz, W. S., Xu, M., Ke, Z., & Luo, J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.033 · Cited by 38 · see citing works
Ablation of glucokinase-expressing tanycytes impacts energy balance and increases adiposity in mice
Rohrbach, A., Caron, É., Dali, R., Brunner, M., Pasquettaz, R., Kolotuev, I., Santoni, F. A., Thorens, B., & Langlet, F. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101311 · Cited by 38 · see citing works
Landry, T., Li, P.-X., Shookster, D., Jiang, Z., Li, H., Laing, B. T., Bunner, W. P., Langton, T., Tong, Q., & Hu, H. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101136 · Cited by 37 · see citing works
Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice
Kumari, R., Paşcalău, R., Wang, H., Bajpayi, S., Yurgel, M. E., Quansah, K. K., Hattar, S. S., Tampakakis, E., & Kuruvilla, R. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113674 · Cited by 37 · see citing works
Ip, C. K., Rezitis, J., Qi, Y., Bajaj, N., Koller, J., Farzi, A., Shi, Y., Tasan, R. O., Zhang, L., & Herzog, H. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.010 · Cited by 35 · see citing works
Self-citationGuo, Q., Chen, N., Patel, K., Wan, M., Zheng, J., & Cao, X. (2023) · Advanced Science · doi:10.1002/advs.202305042 · Cited by 34 · see citing works
Wan, X., Zeng, F., Huang, X., Yang, H.-Q., Wang, L., Shi, Y., Zhang, Z., & Lin, S. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13281 · Cited by 35 · see citing works
Self-citationBrowning of white adipose tissue: role of hypothalamic signaling
Bi, S., & Li, L. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12258 · Cited by 35 · see citing works
Regulation of thermogenic adipocytes during fasting and cold
Reinisch, I., Schreiber, R., & Prokesch, A. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110869 · Cited by 34 · see citing works
Neuropeptide Y in the noradrenergic neurones induces obesity and inhibits sympathetic tone in mice
Vähätalo, L. H., Ruohonen, S. T., Mäkelä, S., Kovalainen, M., Huotari, A., Mäkelä, K. A., Määttä, J. A., Miinalainen, I., Gilsbach, R., Hein, L., et al. (2014) · Acta Physiologica · doi:10.1111/apha.12436 · Cited by 34 · see citing works
mTORC1 in energy expenditure: consequences for obesity
Allard, C., Miralpeix, C., López-Gambero, A. J., & Cota, D. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00934-0 · Cited by 29 · see citing works
Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice
Cheng, L., Yu, Y., Zhang, Q., Szabo, A., Wang, H., & Huang, X. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.04.025 · Cited by 33 · see citing works
Self-citationTovar, S. A., Paeger, L., Heß, S., Morgan, D. A., Hausen, A. C., Brönneke, H. S., Hampel, B., Ackermann, P., Evers, N., Büning, H., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.006 · Cited by 33 · see citing works
Bone-brain interaction: mechanisms and potential intervention strategies of biomaterials
Yu, J., Ji, L., Liu, Y., Wang, X., Wang, J., & Liu, C. (2025) · Bone Research · doi:10.1038/s41413-025-00404-5 · Cited by 34 · see citing works
Wang, D., Yin, J., Zhou, Z., Yan, T., Jia, Y., Jie, H., Zhao, J., Li, R., Li, Y., Guo, C. H., et al. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100315 · Cited by 32 · see citing works
Self-citationEgecioglu, E., Anesten, F., Sch�le, E., & Pálsdóttir, V. (2018) · Biomedical Reports · doi:10.3892/br.2018.1118 · Cited by 31 · see citing works
Klingenspor, M., & Fromme, T. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0965-6_3 · Cited by 30 · see citing works
Shibata, M., Banno, R., Sugiyama, M., Tominaga, T., Onoue, T., Tsunekawa, T., Azuma, Y., Hagiwara, D., Lu, W., Ito, Y., et al. (2016) · Endocrinology · doi:10.1210/en.2015-1430 · Cited by 31 · see citing works
- Authors
- Shi, Y.-C., Lau, J., Lin, Z., Zhang, H., Zhai, L., Sperk, G., Heilbronn, R., Mietzsch, M., Weger, S., Huang, X.-F., Enriquez, R. F., Castillo, L., Baldock, P. A., Zhang, L., Sainsbury, A., Herzog, H., & Lin, S.
- Affiliations
- Garvan Institute of Medical Research (AU)
- Charité – Universitätsmedizin Berlin (DE)
- University of Wollongong (AU)
- The University of Sydney (AU)
- Corresponding author
- Herzog, Herbert
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 17
- Issue
- 2
- Pages
- 236-248
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2002941555
- Cited by
- 266
- References
- 49
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 19 · 2023: 19 · 2022: 13 · 2021: 22 · 2020: 20 · 2019: 16 · 2018: 23 · 2017: 25 · 2016: 21 · 2015: 28 · 2014: 27 · 2013: 8
- FWCI
- 19.45
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-07-02)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Funders
- National Health and Medical Research Council (427661)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- neuropeptide Y, arcuate nucleus, paraventricular nucleus, tyrosine hydroxylase, sympathetic nervous system, brown adipose tissue, thermogenesis, UCP1, Y1 receptor, hypothalamus, locus coeruleus, energy expenditure
- MeSH terms
- Uncoupling Protein 1, Animals, Arcuate Nucleus of Hypothalamus, Adipose Tissue, Brown, Energy Metabolism, Feeding Behavior, Gene Expression Regulation, Glutamate Decarboxylase, Ion Channels, Male, Mice, Inbred C57BL, Neurons, Neuropeptide Y, Oxygen Consumption, Paraventricular Hypothalamic Nucleus, Pro-Opiomelanocortin, RNA, Messenger, Sympathetic Nervous System, Temperature, Tyrosine 3-Monooxygenase, Signal Transduction, Receptors, Neuropeptide Y, Thermogenesis, Models, Animal, Mitochondrial Proteins, Mice, Agouti-Related Protein, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review