Cited by 179Regulation of Appetite and ObesityPharmacology and Obesity TreatmentAdipose Tissue and Metabolism

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RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals

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Chen, Kong Y., Muniyappa, Ranganath, Abel, Brent S., Mullins, Katherine P., Staker, Pamela, Brychta, Robert J., Zhao, Xiongce, Ring, Michael, Psota, Tricia L., Cone, Roger D., Panaro, Brandon L., Gottesdiener, Keith M., Van der Ploeg, Lex H.T., Reitman, Marc L., Skarulis, Monica C.·2015·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2014-4024PMC PMC4399297

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Abstract

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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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: Chen, Kong Y.
Muniyappa, Ranganath
Abel, Brent S.
Brychta, Robert J.
Psota, Tricia L.
Cone, Roger D.
Panaro, Brandon L.
Gottesdiener, Keith M.
Reitman, Marc L.
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
DOI: 10.1210/jc.2014-4024
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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RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals

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