Evidence map›Paper›PMID 39738493›Full record

ArticleInternational journal of obesity (2005)2025

Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity.

Brittany Galuppo, Prabhath Mannam, Jacopo Bonet, Bridget Pierpont, Domenico Trico', Carrie Haskell-Luevano, Mark D Ericson, Katie T Freeman, William M Philbrick, Allen E Bale and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of obesity (2005), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Brittany GaluppoTouro College of Osteopathic Medicine, Middletown, NY, USA.
Prabhath MannamDepartment of Pediatrics, Yale School of Medicine, New Haven, CT, USA.
Jacopo BonetDepartment of Information Engineering, University of Padua, Padova, Italy.ORCID 0000-0003-4097-7943
Bridget PierpontDepartment of Pediatrics, Yale School of Medicine, New Haven, CT, USA.
Domenico Trico'Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID 0000-0002-7633-1346
Carrie Haskell-LuevanoDepartment of Medicinal Chemistry and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Mark D EricsonDepartment of Medicinal Chemistry and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Katie T FreemanDepartment of Medicinal Chemistry and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, USA.
William M PhilbrickDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Allen E BaleDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Sonia CaprioDepartment of Pediatrics, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-7523-5053
Nicola SantoroDepartment of Pediatrics, Yale School of Medicine, New Haven, CT, USA. nicola.santoro@yale.edu.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0M
METABOLIC PREDICTORS AND MARKERS OF CHILDHOOD OBESITYR01HD028016 · NICHD · YALE UNIVERSITY · PI CAPRIO, SONIA · 1991 to 2024
$8.9M
Pathogenesis of youth onset pre-diabetes and Type 2 diabetesR01DK111038 · NIDDK · YALE UNIVERSITY · PI CAPRIO, SONIA · 2016 to 2025
$7.0M
Pathophysiologic mechanisms leading to intrahepatic fat accumulation in obese youthR01MD015974 · NIMHD · YALE UNIVERSITY · PI SANTORO, NICOLA · 2021 to 2025
$3.3M
Melanocortin Receptor Selective LigandsR01DK124504 · NIDDK · UNIVERSITY OF MINNESOTA · PI GIULIANOTTI, MARC, HASKELL-LUEVANO, CARRIE · 2021 to 2024
$2.8M
NCATS NIH HHS UL1 TR001863NICHD NIH HHS R01 HD028016NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK111038NIDDK NIH HHS R01 DK124504NIMHD NIH HHS R01 MD015974
6 · The paper itself

Abstract

backgroundRare variants in melanocortin 4 receptor gene (MC4R) result in a severe form of early-onset obesity; however, it is unclear how these variants may affect abdominal fat distribution, intrahepatic fat accumulation, and related metabolic sequelae.

methodsEight hundred seventy-seven youth (6-21 years) with overweight/obesity, recruited from the Yale Pediatric Obesity Clinic in New Haven, CT, underwent genetic analysis to screen for functionally damaging, rare variants (MAF < 0.01) in MC4R. Participants were assigned to a Pathogenic Variant or No Pathogenic Variant group and completed a 10-timepoint 180-min oral glucose tolerance test (OGTT) and abdominal MRI.

resultsCompared to the No Pathogenic Variant group, the Pathogenic Variant group demonstrated significantly greater glucose concentrations (AUC

conclusionsPathogenic variants in MC4R are associated with increased VAT, HFF%, and insulin resistance, independent from the degree of obesity in youth.

Indexed as

Abdominal FatInsulin ResistancePediatric ObesityReceptor, Melanocortin, Type 4AdolescentChildFemaleGlucose Tolerance TestHumansMaleYoung AdultMC4R protein, humanReceptor, Melanocortin, Type 4

Identifiers

PMID39738493
PMCPMC12095050

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.