The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
The central melanocortin system directly controls peripheral lipid metabolism
Open accessAbstract
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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“while reduced melanocortin signaling promotes insulin sensitivity and glucose uptake in WAT, it reduces glucose utilization in BAT and muscle (131), favoring increased TG synthesis and storage in the body.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [131]
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Rossi, J., Balthasar, N., Olson, D., Scott, M., Berglund, E., Lee, C. E., Choi, M. J., Lauzon, D., Lowell, B. B., & Elmquist, J. K. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.010 · Cited by 672
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Metadata
- 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
- Venue
- Journal of Clinical Investigation
- Published
- 2007-11-01
- Volume
- 117
- Issue
- 11
- Pages
- 3475-3488
- ISSN
- 0021-9738 (ISSN-L)
- 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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