Evidence mapPaperPMID 41828698Full record

ReviewInternational journal of molecular sciences2026

Leptin Receptor b (LEPRb) Mutations Disrupt Hypothalamic Control of the Reproductive Axis.

Athanasios Zikopoulos, Efthalia Moustakli, Periklis Katopodis, Vasilis Sebastian Paraschos, Anastasios Potiris, Ismini Anagnostaki, Aikaterini Lydia Vogiatzoglou, Konstantinos Zacharis, Theodoros Karampitsakos, Konstantinos Zikopoulos and 1 more

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2026. 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

11 authors.

Athanasios ZikopoulosDepartment of Reproductive Medicine and Surgery, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK.ORCID 0009-0002-9553-6803
Efthalia MoustakliDepartment of Nursing, School of Health Sciences, University of Ioannina, 4th Kilometer National Highway Str. Ioannina-Athens, 45500 Ioannina, Greece.ORCID 0009-0005-3333-2620
Periklis KatopodisLaboratory of Medical Genetics in Clinical Practice, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.ORCID 0000-0002-8892-2768
Vasilis Sebastian ParaschosDepartment of Obstetrics and Gynecology, Corewell Health Hospital, 4700 Schaefer Road Suite 310, Dearborn, MI 48126, USA.
Anastasios PotirisThird Department of Obstetrics and Gynecology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.ORCID 0000-0001-7716-1521
Ismini AnagnostakiMedical School, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Aikaterini Lydia VogiatzoglouThird Department of Obstetrics and Gynecology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Konstantinos ZacharisDepartment of Obstetrics and Gynecology, General Hospital of Lamia, 35100 Lamia, Greece.ORCID 0000-0002-3076-818X
Theodoros KarampitsakosThird Department of Obstetrics and Gynecology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.ORCID 0000-0002-4829-9190
Konstantinos ZikopoulosDepartment of Obstetrics & Gynecology, University Hospital of Ioannina, 45500 Ioannina, Greece.ORCID 0000-0002-1350-4182
Sofoklis StavrosThird Department of Obstetrics and Gynecology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adipocytes produce the hormone leptin, a hormone that links energy availability to reproductive function by permitting activation of the hypothalamic-pituitary-gonadal (HPG) axis. Loss-of-function mutations in the long leptin receptor isoform (LEPRb) disrupt intracellular signaling pathways, including the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways, resulting in central leptin resistance and impaired neuroendocrine control of reproduction. Evidence from human monogenic obesity syndromes, animal models, and neuroendocrine studies indicates that LEPRb mutations disrupt hypothalamic circuitry upstream of gonadotropin-releasing hormone (GnRH) neurons, impairing GnRH pulsatility and leading to hypogonadotropic hypogonadism (HH) and infertility. This review synthesizes molecular, translational, and clinical data highlighting the central role of kisspeptin-mediated signaling in leptin-dependent reproductive regulation. Current therapeutic limitations are discussed alongside emerging approaches, including kisspeptin-based therapies and receptor-targeted strategies. Elucidating how LEPRb dysfunction disrupts metabolic-reproductive integration may provide insights into both rare monogenic conditions and common obesity-associated reproductive dysfunction.

Indexed as

HypothalamusMutationReceptors, LeptinReproductionAnimalsGonadotropin-Releasing HormoneHumansHypogonadismHypothalamic-Pituitary-Gonadal AxisKisspeptinsLeptinSignal TransductionGonadotropin-Releasing HormoneKisspeptinsLeptinReceptors, Leptincentral leptin resistancegonadotropin-releasing hormonehypothalamic circuitryinfertilityJAK2/STAT3 signalingKiss1metabolic–reproductive integrationneuroendocrine regulationpubertal failurereceptor signaling defects

Identifiers

PMID41828698
PMCPMC12985556

What Socratic holds

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Registered trials

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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.