The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Open accessAbstract
The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“This notion may explain the importance of UCP2 as a ROS scavenger to keep a physiological ROS level that allows correct NPY and AgRP expression in the hypothalamus ([6](#B6)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139
Ghrelin induces adiposity in rodents
Tschöp, M., Smiley, D. L., & Heiman, M. L. (2000) · Nature · doi:10.1038/35038090 · Cited by 3,949
Self-citationWatterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
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
Self-citationCowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00063-1 · Cited by 1,679
Self-citationAMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637
Superoxide activates mitochondrial uncoupling proteins
Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., Harper, J. A., Roebuck, S. J., Morrison, A., Pickering, S., et al. (2002) · Nature · doi:10.1038/415096a · Cited by 1,382
Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins
Brand, M. D., Affourtit, C., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Pakay, J. L., & Parker, N. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.05.034 · Cited by 1,032
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto, S., Roseberry, A. G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J. M., & Horvath, T. L. (2004) · Science · doi:10.1126/science.1089459 · Cited by 987
Self-citationAbizaid, A., Liu, Z.-W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschöp, M. H., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29867 · Cited by 984
Self-citationZhang, C.-Y., Baffy, G., Perret, P., Krauss, S., Peroni, O., Grujic, D., Hagen, T., Vidal-Puig, A. J., Boss, O., Kim, Y.-B., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00378-6 · Cited by 917
Self-citationGhrelin controls hippocampal spine synapse density and memory performance
Diano, S., Farr, S. A., Benoit, S. C., McNay, E. C., da Silva, I., Horvath, B., Gaskin, F. S., Nonaka, N., Jaeger, L. B., Banks, W. A., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1656 · Cited by 828
Self-citationAMP-activated Protein Kinase Plays a Role in the Control of Food Intake
Andersson-Hall, U. K., Filipsson, K., Abbott, C. R., Woods, A., Smith, K. L., Bloom, S. R., Carling, D., & Small, C. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300557200 · Cited by 777
Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
Parton, L. E., Ye, C. P., Coppari, R., Enriori, P. J., Choi, B., Zhang, C.-Y., Xu, C., Vianna, C. R., Balthasar, N., Lee, C. E., et al. (2007) · Nature · doi:10.1038/nature06098 · Cited by 700
Yamagishi, S., Edelstein, D., Du, X.-L., Kaneda, Y., Guzmán, M., & Brownlee, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007383200 · Cited by 622
Willesen, M. G., Kristensen, P., & Rømer, J. (1999) · Neuroendocrinology · doi:10.1159/000054491 · Cited by 605
Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis
Bergeron, R., Ren, J. M., Cadman, K. S., Moore, I. K., Perret, P., Pypaert, M., Young, L. H., Semenkovich, C. F., & Shulman, G. I. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.6.e1340 · Cited by 561
Self-citationHypothalamic sensing of fatty acids
Lam, T. K. T., Schwartz, G. J., & Rossetti, L. (2005) · Nature Neuroscience · doi:10.1038/nn1456 · Cited by 478
Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C. S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C. A., Roberts, J. L., et al. (2007) · Nature Medicine · doi:10.1038/nm1525 · Cited by 416
Self-citationSCOTT, I. D., & Nicholls, D. G. (1980) · Biochemical Journal · doi:10.1042/bj1860021 · Cited by 394
Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H., & Wakabayashi, I. (2000) · Endocrinology · doi:10.1210/endo.141.12.7920 · Cited by 379
The role of AMP‐activated protein kinase in mitochondrial biogenesis
Reznick, R. M., & Shulman, G. I. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109512 · Cited by 375
Self-citationAblation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice
Sun, Y., Asnicar, M., Saha, P., Chan, L., & Smith, R. G. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.004 · Cited by 358
Du, X., Edelstein, D., Obici, S., Higham, N., Zou, M., & Brownlee, M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci23354 · Cited by 351
Zhang, C., Parton, L. E., Ye, C. P., Krauss, S., Shen, R., Lin, C.-T., Porco, J. A. J., & Lowell, B. B. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.010 · Cited by 337
Horváth, T. L., Bechmann, I., Naftolin, F. N., Kalra, S. P., & Léránth, C. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00184-4 · Cited by 301
Coppola, A., Liu, Z.-W., Andrews, Z. B., Paradis, E., Roy, M.-C., Friedman, J. M., Ricquier, D., Richard, D., Horvath, T. L., Gao, X.-B., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.002 · Cited by 295
Self-citationBarazzoni, R., Bosutti, A., Stebel, M., Cattin, M. R., Roder, E., Visintin, L., Cattin, L., Biolo, G., Zanetti, M., & Guarnieri, G. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00115.2004 · Cited by 256
Input organization and plasticity of hypocretin neurons
Horváth, T. L., & Gao, X. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.03.003 · Cited by 198
Self-citationDiano, S., Matthews, R. T., Patrylo, P. R., Yang, L., Beal, M. F., Barnstable, C. J., & Horváth, T. L. (2003) · Endocrinology · doi:10.1210/en.2003-0667 · Cited by 191
Self-citationHorvath, T. L., Warden, C. H., Hajós, M., Lombardi, A., Goglia, F., & Diano, S. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-23-10417.1999 · Cited by 181
Self-citationKrauss, S., Zhang, C., & Lowell, B. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012410699 · Cited by 176
NPY/AgRP neurons are not essential for feeding responses to glucoprivation
Luquet, S. H., Phillips, C. T., & Palmiter, R. D. (2006) · Peptides · doi:10.1016/j.peptides.2006.08.036 · Cited by 147
Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons
Kohno, D., Sone, H., Minokoshi, Y., & Yada, T. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.11.166 · Cited by 138
Tsubone, T., Masaki, T., Katsuragi, I., Tanaka, K., Kakuma, T., & Yoshimatsu, H. (2005) · Regulatory Peptides · doi:10.1016/j.regpep.2005.04.004 · Cited by 130
Regulation of hypothalamic malonyl-CoA by central glucose and leptin
Wolfgang, M. J., Cha, S. H., Sidhaye, A., Chohnan, S., Cline, G., Shulman, G. I., & Lane, M. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709778104 · Cited by 127
Self-citationThoughts for Food: Brain Mechanisms and Peripheral Energy Balance
Abizaid, A. B., Gao, Q., & Horváth, T. L. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.025 · Cited by 122
Garcia‐Martínez, C., Sibille, B., Solanes, G., Darimont, C., Macé, K., Villarroya, F., & Gómez-Foix, A. M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0828fje · Cited by 101
Rossmeisl, M., Barbatelli, G., Flachs, P., Brauner, P., Zingaretti, M. C., Marelli, M., Janovská, P., Horáková, M., Syrový, I., Cinti, S., et al. (2002) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2002.02627.x · Cited by 75
Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold
Horváth, B., Spies, C., Horváth, G., Kox, W. J., Miyamoto, S., Barry, S. J., Warden, C. H., Bechmann, I., Diano, S., Heemskerk, J., et al. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01167-x · Cited by 37
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
Metformin—mode of action and clinical implications for diabetes and cancer
Pernicova, I., & Korbonits, M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.256 · Cited by 1,393
Mitochondrial ROS Signaling in Organismal Homeostasis
Shadel, G. S., & Horvath, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.10.001 · Cited by 1,353
Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J., Batterham, R. L., Benoit, S. C., Bowers, C. Y., Broglio, F., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.005 · Cited by 1,034
Self-citationDeconstruction of a neural circuit for hunger
Atasoy, D., Betley, J. N., Su, H. H., & Sternson, S. M. (2012) · Nature · doi:10.1038/nature11270 · Cited by 969
Metadata
- Authors
- Andrews, Z. B., Liu, Z.-W., Walllingford, N., Erion, D. M., Borok, E., Friedman, J. M., Tschöp, M. H., Shanabrough, M., Cline, G., Shulman, G. I., Coppola, A., Gao, X.-B., Horvath, T. L., & Diano, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Hubei University of Medicine (CN)
- University of Cincinnati (US)
- Yale University (US)
- Corresponding author
- Diano, Sabrina
- ORCID
- Venue
- Nature
- Published
- 2008-07-30
- Volume
- 454
- Issue
- 7206
- Pages
- 846-851
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4101536
- OpenAlex
- W1988803699
- Cited by
- 710
- References
- 40
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 21 · 2023: 21 · 2022: 33 · 2021: 31 · 2020: 25 · 2019: 23 · 2018: 40 · 2017: 55 · 2016: 42 · 2015: 39 · 2014: 51 · 2013: 69 · 2012: 66
- FWCI
- 23.63
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-06-04)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG022880)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK040936)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, UCP2, NPY/AgRP neurons, arcuate nucleus, hypothalamus, mitochondrial respiration, mitochondrial proliferation, fatty acid oxidation, AMPK, carnitine palmitoyltransferase 1, free radicals, oxidative stress, proopiomelanocortin neurons, synaptic plasticity, dietary intake, appetite regulation, G protein-coupled receptor signaling
- MeSH terms
- Uncoupling Protein 2, Animals, Carnitine O-Palmitoyltransferase, Fatty Acids, Feeding Behavior, Gene Expression Regulation, Hypothalamus, Ion Channels, Mitochondria, Neurons, Neuropeptide Y, Phosphorylation, Synapses, Reactive Oxygen Species, Mitochondrial Proteins, Mice, Membrane Potential, Mitochondrial, Agouti-Related Protein, Ghrelin
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
