Evidence map›Paper›PMID 34097736›Full record

ArticleThe Journal of clinical endocrinology and metabolism2021

Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity.

Sophie Courbage, Christine Poitou, Johanne Le Beyec-Le Bihan, Alexandra Karsenty, Julie Lemale, Véronique Pelloux, Jean-Marc Lacorte, Jean-Claude Carel, Nathalie Lecomte, Caroline Storey and 6 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07302802 (Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice), which is not on this map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 7% of its field
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.

NCT07302802 recruitingstarted 2025, after this paper: background citation

Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice

Ran2025Enrolled70Registered outcomes2Posted comparisons0ConditionsMonogenic ObesityArmsSemaglutide (administered by PDS290 pen-injector)
PMID 34291582PMID 35528826PMID 28377240PMID 33205056other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Classification of Congenital Leptin Deficiency.The Journal of clinical endocrinology and metabolism · 2024
    Pooled it
  3. Monoallelic pathogenic variants in LEPR do not cause obesity.American journal of human genetics · 2024
    Trial
  4. Article
  5. Article
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  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Melanocortin 4 receptor mutation in obesity.World journal of experimental medicine · 2024
    Review
  15. Article
  16. Review
  17. Article
  18. Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar.The Journal of clinical endocrinology and metabolism · 2023
    Article
  19. Article
  20. 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

16 authors at 3 institutions in 1 country.

Sophie CourbageAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Pediatric Nutrition and Gastroenterology Department, Armand-Trousseau Hospital, Sorbonne University, Paris, France.ORCID 0000-0002-6581-4107
Christine PoitouAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France.ORCID 0000-0001-7769-6331
Johanne Le Beyec-Le BihanAssistance Publique-Hôpitaux de Paris (AP-HP), Endocrine and Oncological Biochemistry Department, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.ORCID 0000-0002-5647-2002
Alexandra KarsentyAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Pediatric Nutrition and Gastroenterology Department, Armand-Trousseau Hospital, Sorbonne University, Paris, France.
Julie LemaleAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Pediatric Nutrition and Gastroenterology Department, Armand-Trousseau Hospital, Sorbonne University, Paris, France.ORCID 0000-0002-4979-1822
Véronique PellouxSorbonne Université, INSERM, Nutrition and Obesities; Systemic Approaches (NutriOmics) Research Unit, Paris, France.
Jean-Marc LacorteAssistance Publique-Hôpitaux de Paris (AP-HP), Endocrine and Oncological Biochemistry Department, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
Jean-Claude CarelUniversité de Paris, F-75019, Paris, France; AP-HP.Nord Université de Paris. Hôpital Universitaire Robert-Debré, Service d'Endocrinologie Diabétologie Pédiatrique F-75019, Paris, France.ORCID 0000-0002-0424-6767
Nathalie LecomteUniversité de Paris, F-75019, Paris, France; AP-HP.Nord Université de Paris. Hôpital Universitaire Robert-Debré, Service d'Endocrinologie Diabétologie Pédiatrique F-75019, Paris, France.
Caroline StoreyUniversité de Paris, F-75019, Paris, France; AP-HP.Nord Université de Paris. Hôpital Universitaire Robert-Debré, Service d'Endocrinologie Diabétologie Pédiatrique F-75019, Paris, France.
Gianpaolo De FilippoUniversité de Paris, F-75019, Paris, France; AP-HP.Nord Université de Paris. Hôpital Universitaire Robert-Debré, Service d'Endocrinologie Diabétologie Pédiatrique F-75019, Paris, France.ORCID 0000-0003-1313-5599
Muriel CoupayeAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France.
Jean-Michel OppertAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France.ORCID 0000-0003-0324-4820
Patrick TounianAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Pediatric Nutrition and Gastroenterology Department, Armand-Trousseau Hospital, Sorbonne University, Paris, France.ORCID 0000-0002-5976-2240
Karine ClémentAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France.ORCID 0000-0003-4619-6785
Béatrice DubernAssistance Publique-Hôpitaux de Paris (AP-HP), Reference Centre for Rare Diseases (PRADORT, Prader-Willi Syndrome and other Rare Forms of Obesity with Eating Behavior Disorders), Pediatric Nutrition and Gastroenterology Department, Armand-Trousseau Hospital, Sorbonne University, Paris, France.ORCID 0000-0003-2614-7556
Inserm · FRSorbonne Université · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextUnlike homozygous variants, the implication of heterozygous variants on the leptin-melanocortin pathway in severe obesity has not been established.

objectiveTo describe the frequency, the phenotype, and the genotype-phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity.

methodsIn this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities.

resultsThe frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P < .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P < .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P < .01). In children, no significant differences were found for the age of obesity onset and BMI.

conclusionHeterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.

Indexed as

AdultAge of OnsetBody Mass IndexChildFemaleGenetic Association StudiesGenetic VariationHeterozygoteHomozygoteHumansLeptinMaleObesity, MorbidPhenotypePro-OpiomelanocortinProprotein Convertase 1LEP protein, humanLEPR protein, humanLeptinPCSK1 protein, humanPro-OpiomelanocortinProprotein Convertase 1Receptors, Leptinleptinmelanocortin pathwayonset obesitySevere early

Identifiers

PMID34097736
OpenAlexW3172553412

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Registered trials

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 OpenQuestion graph.