Cited by 396Regulation of Appetite and ObesityAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

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The central melanocortin system directly controls peripheral lipid metabolism

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Nogueiras, Ruben, Wiedmer, Petra, Perez-Tilve, Diego, Veyrat-Durebex, Christelle, Keogh, Julia M., Sutton, Gregory M., Pfluger, Paul T., Castaneda, Tamara R., Neschen, Susanne, Hofmann, Susanna M., Howles, Philip N., Morgan, Donald A., Benoit, Stephen C., Szanto, Ildiko, Schrott, Brigitte, Schürmann, Annette, Joost, Hans-Georg, Hammond, Craig, Hui, David Y., Woods, Stephen C., Rahmouni, Kamal, Butler, Andrew A., Farooqi, I. Sadaf, O’Rahilly, Stephen, Rohner-Jeanrenaud, Françoise, Tschöp, Matthias H.·2007·Journal of Clinical Investigation

DOI 10.1172/jci31743PMC PMC1978426

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Abstract

Disruptions of the melanocortin signaling system have been linked to obesity. We investigated a possible role of the central nervous melanocortin system (CNS-Mcr) in the control of adiposity through effects on nutrient partitioning and cellular lipid metabolism independent of nutrient intake. We report that pharmacological inhibition of melanocortin receptors (Mcr) in rats and genetic disruption of Mc4r in mice directly and potently promoted lipid uptake, triglyceride synthesis, and fat accumulation in white adipose tissue (WAT), while increased CNS-Mcr signaling triggered lipid mobilization. These effects were independent of food intake and preceded changes in adiposity. In addition, decreased CNS-Mcr signaling promoted increased insulin sensitivity and glucose uptake in WAT while decreasing glucose utilization in muscle and brown adipose tissue. Such CNS control of peripheral nutrient partitioning depended on sympathetic nervous system function and was enhanced by synergistic effects on liver triglyceride synthesis. Our findings offer an explanation for enhanced adiposity resulting from decreased melanocortin signaling, even in the absence of hyperphagia, and are consistent with feeding-independent changes in substrate utilization as reflected by respiratory quotient, which is increased with chronic Mcr blockade in rodents and in humans with loss-of-function mutations in MC4R. We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity.

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Metabolism of Isolated Fat Cells
Rodbell, M. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51687-2 · Cited by 4,647
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
Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase
Zimmermann, R., Bogner‐Strauß, J. G., Haemmerle, G., Schoiswohl, G., Birner‐Gruenberger, R., Riederer, M., Lass, A., Neuberger, G., Eisenhaber, F., Hermetter, A., et al. (2004) · Science · doi:10.1126/science.1100747 · Cited by 2,121
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
Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
Farooqi, I. S., Keogh, J. M., Yeo, G. S. H., Lank, E. J., Cheetham, T., & O'Rahilly, S. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022050 · Cited by 1,778
Self-citation
Anatomy and regulation of the central melanocortin system
Cone, R. D. (2005) · Nature Neuroscience · doi:10.1038/nn1455 · Cited by 1,583
METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS.
Rodbell, M. (1964) · PubMed · Cited by 1,387
A frameshift mutation in MC4R associated with dominantly inherited human obesity
Yeo, G. S. H., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., & O'Rahilly, S. (1998) · Nature Genetics · doi:10.1038/2404 · Cited by 1,159
Self-citation
NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates
Luquet, S. H., Perez, F. A., Hnasko, T. S., & Palmiter, R. D. (2005) · Science · doi:10.1126/science.1115524 · Cited by 1,150
Obesity Wars
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,124

Flagged first, then by citations

Show all 71 references

Research works printed but not linked: 4

Aja, 2006, Adv. Psychosom. Med., 27, 1
Frigeri, 1988, Int. J. Obes., 12, 305
Appel, 1992, Am. J. Physiol., 262, E695
10.1172/JCI200421737 · DOI

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Items 201–300 of 394

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Zhang, Y., Rodrigues, E., Gao, Y., King, M., Cheng, K., Erdös, B., Tümer, N., Carter, C., & Scarpace, P. J. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.06.001 · Cited by 26
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Sevilla, F. E., Pérez-Navarro, M. J., Muñoz-Pasadas, M., Sáez‐Zea, C., Katati, M. J., Maroto, G. P., Ramírez-Navarro, Á., & Mínguez‐Castellanos, A. (2011) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2010.01469.x · Cited by 26
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Basu, R., & Flak, J. N. (2024) · Vitamins and hormones · doi:10.1016/bs.vh.2024.07.004 · Cited by 12
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Almundarij, T. I., Smyers, M. E., Spriggs, A., Heemstra, L. A., Beltz, L. A., Dyne, E. D., Ridenour, C., & Novak, C. M. (2016) · Scientific Reports · doi:10.1038/srep37435 · Cited by 11
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Mul, J. D., O’Duibhir, E., Shrestha, Y. B., Koppen, A., Vargovič, P., Toonen, P. W., Zarebidaki, E., Květňanský, R., Kalkhoven, E., Cuppen, E. P. J. G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060214 · Cited by 11
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Møller, C. L., Kjøbsted, R., Enriori, P. J., Jensen, T. E., Garcia‐Rudaz, C., Litwak, S. A., Raun, K., Wojtaszewski, J. F. P., Wulff, B. S., & Cowley, M. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157027 · Cited by 12
Brain lipid sensing and the neural control of energy balance
Cruciani‐Guglielmacci, C., Stunff, H. L., & Magnan, C. (2024) · Biochimie · doi:10.1016/j.biochi.2024.05.020 · Cited by 13
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Retracted
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Yang, J., Gao, Q., Gao, X., Tao, X., Cai, H., Fan, Y., Zhang, N., Zhang, Y., Li, L., & Li, H. (2016) · PubMed · doi:10.6133/apjcn.2016.25.1.18 · Cited by 10
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Weeden, T., Stefano, J., Duan, S., Edling, A. E., Hou, L., Chuang, W., Perricone, M. A., Pan, C. Q., & Dzuris, J. L. (2010) · Journal of Peptide Science · doi:10.1002/psc.1306 · Cited by 9
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Brénachot, X., Gautier, T., Nédélec, E., Deckert, V., Laderrière, A., Nuzzaci, D., Rigault, C., Lemoine, A., Pénicaud, L., Lagrost, L., et al. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00245 · Cited by 9
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Gavini, C. K., Britton, S. L., Koch, L. G., & Novak, C. M. (2018) · Obesity · doi:10.1002/oby.22166 · Cited by 9
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Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking
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Yan, Y. J., Tian, L., Xiang, X., Ding, W. J., Song, G., & Xu, J. (2015) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2015.1069391 · Cited by 7
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de Backer, M. W. A., la Fleur, S. E., & Adan, R. A. H. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.12.021 · Cited by 7
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Derkach, K. V., Shpakova, E. A., Жарова, О. А., & Shpakov, A. O. (2014) · Doklady Biochemistry and Biophysics · doi:10.1134/s1607672914050019 · Cited by 6
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Authors: Nogueiras, R., Wiedmer, P., Perez-Tilve, D., Veyrat-Durebex, C., Keogh, J. M., Sutton, G. M., Pfluger, P. T., Castaneda, T. R., Neschen, S., Hofmann, S. M., Howles, P. N., Morgan, D. A., Benoit, S. C., Szanto, I., Schrott, B., Schürmann, A., Joost, H.-G., Hammond, C., Hui, D. Y., Woods, S. C., Rahmouni, K., Butler, A. A., Farooqi, I. S., O’Rahilly, S., Rohner-Jeanrenaud, F., & Tschöp, M. H.
Affiliations: German Institute of Human Nutrition (DE)
Addenbrooke's Hospital (GB)
Pennington Biomedical Research Center (US)
University of Cincinnati (US)
University of Iowa (US)
Eli Lilly (United States) (US)
Corresponding author: Tschöp, Matthias H.
ORCID: Wiedmer, Petra
Keogh, Julia M.
Pfluger, Paul T.
Hofmann, Susanna M.
Morgan, Donald A.
Schürmann, Annette
Joost, Hans-Georg
Hui, David Y.
Woods, Stephen C.
Rahmouni, Kamal
Butler, Andrew A.
Farooqi, I. Sadaf
O’Rahilly, Stephen
Tschöp, Matthias H.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2007-11-01
Volume: 117
Issue: 11
Pages: 3475-3488
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci31743
PMC: PMC1978426
OpenAlex: W2151831322
Cited by: 396
References: 71
Citations by year: 2026: 4 · 2025: 14 · 2024: 11 · 2023: 9 · 2022: 9 · 2021: 10 · 2020: 19 · 2019: 17 · 2018: 16 · 2017: 25 · 2016: 26 · 2015: 27 · 2014: 24 · 2013: 29 · 2012: 36
FWCI: 10.61
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
University of Cincinnati
Wellcome Trust (068086)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (105889, 3100A0)
Medical Research Council
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: melanocortin system, melanocortin-4 receptor, obesity, lipid metabolism, white adipose tissue, nutrient partitioning, triglyceride synthesis, lipid mobilization, insulin sensitivity, glucose uptake, brown adipose tissue, sympathetic nervous system, respiratory quotient, loss-of-function mutations
MeSH terms: Adipose Tissue, alpha-MSH, Animals, Behavior, Animal, Central Nervous System, Eating, Glucose, Humans, Insulin, Melanocyte-Stimulating Hormones, Signal Transduction, Rats, Sprague-Dawley, Adipocytes, Mice, Knockout, Receptors, Melanocortin, Receptor, Melanocortin, Type 4, Lipid Metabolism, Mice, Rats, Melanocortins

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The central melanocortin system directly controls peripheral lipid metabolism

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