The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals
Open accessAbstract
CONTEXT: Activation of the melanocortin-4 receptor (MC4R) with the synthetic agonist RM-493 decreases body weight and increases energy expenditure (EE) in nonhuman primates. The effects of MC4R agonists on EE in humans have not been examined to date. OBJECTIVE, DESIGN, AND SETTING: In a randomized, double-blind, placebo-controlled, crossover study, we examined the effects of the MC4R agonist RM-493 on resting energy expenditure (REE) in obese subjects in an inpatient setting. STUDY PARTICIPANTS AND METHODS: Twelve healthy adults (6 men and 6 women) with body mass index of 35.7 ± 2.9 kg/m(2) (mean ± SD) received RM-493 (1 mg/24 h) or placebo by continuous subcutaneous infusion over 72 hours, followed immediately by crossover to the alternate treatment. All subjects received a weight-maintenance diet (50% carbohydrate, 30% fat, and 20% protein) and performed 30 minutes of standardized exercise daily. Continuous EE was measured on the third treatment day in a room calorimeter, and REE in the fasting state was defined as the mean of 2 30-minute resting periods. RESULTS: RM-493 increased REE vs placebo by 6.4% (95% confidence interval, 0.68-13.02%), on average by 111 kcal/24 h (95% confidence interval, 15-207 kcal, P = .03). Total daily EE trended higher, whereas the thermic effect of a test meal and exercise EE did not differ significantly. The 23-hour nonexercise respiratory quotient was lower during RM-493 treatment (0.833 ± 0.021 vs 0.848 ± 0.022, P = .02). No adverse effect on heart rate or blood pressure was observed. CONCLUSIONS: Short-term administration of the MC4R agonist RM-493 increases REE and shifts substrate oxidation to fat in obese individuals.
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“In another study [80], setmelanotide administration for 3 days to 12 in obese adults caused significant increases in resting energy expenditure and preferential increases in fat oxidation without raising BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [80]
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“In another study [80], setmelanotide administration for 3 days to 12 in obese adults caused significant increases in resting energy expenditure and preferential increases in fat oxidation without raising BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [80]
In the citing paper
“In another study [80], setmelanotide administration for 3 days to 12 in obese adults caused significant increases in resting energy expenditure and preferential increases in fat oxidation without raising BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [80]
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Cites
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RetractedRole of melanocortinergic neurons in feeding and the agouti obesity syndrome
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Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity
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Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ
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Studies on the Physiological Functions of the Melanocortin System
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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
The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology
Tao, Y.-X. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0037 · Cited by 531
Modulation of Blood Pressure by Central Melanocortinergic Pathways
Greenfield, J. R., Miller, J. W., Keogh, J. M., Henning, E., Satterwhite, J. H., Cameron, G. S., Astruc, B., Mayer, J. P., Brage, S., See, T. C., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0803085 · Cited by 477
The Central Melanocortin System and Energy Homeostasis
Cone, R. D. (1999) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(99)00153-8 · Cited by 351
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Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist
Kühnen, P., Clément, K., Wiegand, S., Blankenstein, O., Gottesdiener, K., Martini, L. L., Mai, K., Blume-Peytavi, U., Grüters, A., & Krude, H. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1512693 · Cited by 485
Self-citationMelanocortin-4 receptor–regulated energy homeostasis
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Metadata
- Authors
- Chen, K. Y., Muniyappa, R., Abel, B. S., Mullins, K. P., Staker, P., Brychta, R. J., Zhao, X., Ring, M., Psota, T. L., Cone, R. D., Panaro, B. L., Gottesdiener, K. M., Van der Ploeg, L. H. T., Reitman, M. L., & Skarulis, M. C.
- Affiliations
- National Institutes of Health (US)
- Vanderbilt University (US)
- Rhythm (United states) (US)
- Rhythm Pharmaceuticals (K.M.G., L.H.T.V.d.P.), Boston, Massachusetts 02116
- Corresponding author
- Skarulis, Monica C.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-04-01
- Volume
- 100
- Issue
- 4
- Pages
- 1639-1645
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4399297
- OpenAlex
- W2079643489
- Cited by
- 174
- References
- 30
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 21 · 2020: 22 · 2019: 21 · 2018: 21 · 2017: 16 · 2016: 18 · 2015: 6
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (MD 20892)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK070332, P30DK058404)
- NIH Clinical Center
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- melanocortin-4 receptor agonist, resting energy expenditure, obesity, energy expenditure, substrate oxidation, respiratory quotient, weight loss, continuous subcutaneous infusion, thermogenesis
- MeSH terms
- Adult, alpha-MSH, Combined Modality Therapy, Double-Blind Method, Energy Metabolism, Female, Humans, Male, Middle Aged, Obesity, Rest, Cross-Over Studies, Anti-Obesity Agents, Receptor, Melanocortin, Type 4, Young Adult, Weight Reduction Programs
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