The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Interactions Between the Melanocortin System and Leptin in Control of Sympathetic Nerve Traffic
Abstract
Leptin plays an important role in regulation of body weight through regulation of food intake and sympathetically mediated thermogenesis. The hypothalamic melanocortin system, via activation of the melanocortin-4 receptor (MC4-R), decreases appetite and weight, but its effects on sympathetic nerve activity (SNA) are unknown. In addition, it is not known whether sympathoactivation to leptin is mediated by the melanocortin system. We tested the interactions between these systems in regulation of brown adipose tissue (BAT) and renal and lumbar SNA in anesthetized Sprague-Dawley rats. Intracerebroventricular administration of the MC4-R agonist MT-II (200 to 600 pmol) produced a dose-dependent sympathoexcitation affecting BAT and renal and lumbar beds. This response was completely blocked by the MC4-R antagonist SHU9119 (30 pmol ICV). Administration of leptin (1000 microg/kg IV) slowly increased BAT SNA (baseline, 41+/-6 spikes/s; 6 hours, 196+/-28 spikes/s; P=0.001) and renal SNA (baseline, 116+/-16 spikes/s; 6 hours, 169+/-26 spikes/s; P=0.014). Intracerebroventricular administration of SHU9119 did not inhibit leptin-induced BAT sympathoexcitation (baseline, 35+/-7 spikes/s; 6 hours, 158+/-34 spikes/s; P=0.71 versus leptin alone). However, renal sympathoexcitation to leptin was completely blocked by SHU9119 (baseline, 142+/-17 spikes/s; 6 hours, 146+/-25 spikes/s; P=0.007 versus leptin alone). This study demonstrates that the hypothalamic melanocortin system can act to increase sympathetic nerve traffic to thermogenic BAT and other tissues. Our data also suggest that leptin increases renal SNA through activation of hypothalamic melanocortin receptors. In contrast, sympathoactivation to thermogenic BAT by leptin appears to be independent of the melanocortin system.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“In addition, ICV injections of MC4R agonist increased brown adipose tissue (BAT) and lumbar SNS activity whereas MC4R blockade completely abolished these effects [39].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [39]
In the citing paper
“In addition, ICV injections of MC4R agonist increased brown adipose tissue (BAT) and lumbar SNS activity whereas MC4R blockade completely abolished these effects [39].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [39]
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,924
Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G. E., & Grüters, A. (1998) · Nature Genetics · doi:10.1038/509 · Cited by 1,769
Identification of targets of leptin action in rat hypothalamus.
Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118891 · Cited by 1,499
The role of neuropeptide Y in the antiobesity action of the obese gene product
Stephens, T. W., Basinski, M., Bristow, P. K., Bue-Valleskey, J. M., Burgett, S. G., Craft, L., Hale, J., Hoffmann, J., Hsiung, H. M., Kriauciunas, A., et al. (1995) · Nature · doi:10.1038/377530a0 · Cited by 1,498
Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor
Lu, D., Willard, D. H., Patel, I. R., Kadwell, S. H., Overton, L. K., Kost, T., Luther, M., Chen, W., Woychik, R. P., Wilkison, W. O., et al. (1994) · Nature · doi:10.1038/371799a0 · Cited by 1,075
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8878 · Cited by 1,033
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979
Leptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G. (1997) · Diabetes · doi:10.2337/diab.46.12.2119 · Cited by 879
Attenuation of the Obesity Syndrome of ob/ob Mice by the Loss of Neuropeptide Y
Erickson, J. C., Hollopeter, G., & Palmiter, R. D. (1996) · Science · doi:10.1126/science.274.5293.1704 · Cited by 804
Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus
Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.10.5570 · Cited by 769
Leptin Is a Metabolic Gate for the Onset of Puberty in the Female Rat
Cheung, C. C., Thornton, J. E., Kuijper, J. L., Weigle, D. S., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.2.5054 · Cited by 534
Melanocortin receptors in leptin effects
Seeley, R. J., Yagaloff, K. A., Fisher, S. L., Burn, P., Thiele, T. E., van Dijk, G., Baskin, D. G., & Schwartz, M. W. (1997) · Nature · doi:10.1038/37016 · Cited by 522
Role of leptin in fat regulation
Collins, S., Kuhn, C. M., Petro, A. E., Swick, A. G., Chrunyk, B. A., & Surwit, R. S. (1996) · Nature · doi:10.1038/380677a0 · Cited by 520
Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice
Thornton, J. E., Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.11.5651 · Cited by 437
Comuzzie, A. G., Hixson, J. E., Almasy, L. A., Mitchell, B. D., Mahaney, M. C., Dyer, T. D., Stern, M. P., MacCluer, J. W., & Blangero, J. (1997) · Nature Genetics · doi:10.1038/ng0397-273 · Cited by 430
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
Effect of chronic hypertension and sympathetic denervation on wall/lumen ratio of cerebral vessels.
Hart, M. N., Heistad, D. D., & Brody, M. J. (1980) · Hypertension · doi:10.1161/01.hyp.2.4.419 · Cited by 257
Independent and Additive Effects of Central POMC and Leptin Pathways on Murine Obesity
Boston, B. A., Blaydon, K. M., Varnerin, J. P., & Cone, R. D. (1997) · Science · doi:10.1126/science.278.5343.1641 · Cited by 239
Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system
Satoh, N., Ogawa, Y., Katsuura, G., Numata, Y., Masuzaki, H., Yoshimasa, Y., & Nakao, K. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00401-7 · Cited by 188
Thiele, T. E., van Dijk, G., Yagaloff, K. A., Fisher, S. L., Schwartz, M. W., Burn, P., & Seeley, R. J. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.1.r248 · Cited by 177
Chagnon, Y. C., Chen, W., Përusse, L., Chagnon, M., Nadeau, A., Wilkison, W. O., & Bouchard, C. (1997) · Molecular Medicine · doi:10.1007/bf03401705 · Cited by 159
Intracerebroventricular insulin produces nonuniform regional increases in sympathetic nerve activity
Muntzel, M. S., Morgan, D. A., Mark, A. L., & Johnson, A. K. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.5.r1350 · Cited by 134
Kask, A., Rägo, L., Mutulis, F., Pähkla, R., Wikberg, J. E. S., & Schiöth, H. B. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8389 · Cited by 129
Nonuniform regional sympathetic nerve responses to hyperinsulinemia in rats
Morgan, D. A., Balon, T. W., Ginsberg, B. H., & Mark, A. L. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.2.r423 · Cited by 92
Schiöth, H. B., Muceniece, R., Mutulis, F., Prūsis, P., Lindeberg, G., Sharma, S. D., Hruby, V. J., & Wikberg, J. E. S. (1997) · Peptides · doi:10.1016/s0196-9781(97)00079-x · Cited by 87
Receptors for the melanocortin peptides in the central nervous system
Low, M. J., Simerly, R. B., & Cone, R. D. (1994) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-199400010-00016 · Cited by 57
Effects of preoptic microinjections of α-MSH on fever and normal temperature control in rabbits
Feng, J., Dao, T., & Lipton, J. M. (1987) · Brain Research Bulletin · doi:10.1016/0361-9230(87)90111-0 · Cited by 52
Sympathetic Nervous System Influences on tne Kidney
DiBona, G. F. (1989) · American Journal of Hypertension · doi:10.1093/ajh/2.3.119s · Cited by 47
Effects of a potent melanocortin agonist on the diabetic/obese phenotype in yellow mice
Zemel, M. B., Moore, J. B., Moustaïd, N., Kim, J., Nichols, J., Blanchard, S., Parks, D., Harris, C. O., Lee, F., Grizzle, M. K., et al. (1998) · International Journal of Obesity · doi:10.1038/sj.ijo.0800630 · Cited by 18
Research works printed but not linked: 2
- Egawa M, Yoshimatsu H, Bray GA. Preoptic area injection of corticotrophin-releasing hormone stimulates sympathetic activity. Am J Physiol. 1990;259:R799–R806.
- Morgan DA, Thorén P, Staudt SM, Mark AL. Differential effects of anesthesia on heart rate (HR), renal (RSNA), and lumbar sympathetic nerve activity (LSNA) in the rat. FASEB J. 1988;2:A1690. Abstract.
Cited by
Sorted by citations
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
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
The Kidney, Hypertension, and Obesity
Hall, J. E. (2003) · Hypertension · doi:10.1161/01.hyp.0000052314.95497.78 · Cited by 868
Integration of NPY, AGRP, and Melanocortin Signals in the Hypothalamic Paraventricular Nucleus
Cowley, M. A., Pronchuk, N., Fan, W., Dinulescu, D. M., Colmers, W. F., & Cone, R. D. (1999) · Neuron · doi:10.1016/s0896-6273(00)80829-6 · Cited by 612
Studies on the Physiological Functions of the Melanocortin System
Cone, R. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0034 · Cited by 615
Metadata
- Authors
- Haynes, W. G., Morgan, D. A., Djalali, A., Sivitz, W. I., & Mark, A. L.
- Affiliations
- University of Iowa (US)
- Venue
- Hypertension
- Published
- 1999-01
- Volume
- 33
- Issue
- 1
- Pages
- 542-547
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2038872854
- Cited by
- 358
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 12 · 2017: 13 · 2016: 13 · 2015: 10 · 2014: 22 · 2013: 17 · 2012: 5
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Pharmaceutical Research and Manufacturers of America Foundation
- National Institutes of Health (5p50hl044546-05, 5r29hl043514-05)
- National Heart, Lung, and Blood Institute (HL-43514, HL-14388, HL-44546, P01HL014388)
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- melanocortin system, leptin, melanocortin-4 receptor, sympathetic activity, brown adipose tissue, thermogenesis, renal sympathetic nerve activity, lumbar sympathetic nerve activity, hypothalamus, melanotan II, SHU9119, appetite regulation, body weight regulation
- MeSH terms
- Animals, Adipose Tissue, Brown, Cerebral Ventricles, Infusions, Intravenous, Injections, Intraventricular, Kidney, Male, Melanocyte-Stimulating Hormones, Proteins, Recombinant Proteins, Sympathetic Nervous System, Rats, Sprague-Dawley, Receptors, Corticotropin, Leptin, Receptor, Melanocortin, Type 4, Rats
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
