Evidence map›Paper›PMID 39611214›Full record

ArticleDiabetes, obesity & metabolism2025

Hepatic lipogenesis marked by GCKR-modulated triglycerides increases serum FGF21 in children/teens with obesity.

Claudio Maffeis, Anita Morandi, Chiara Zusi, Francesca Olivieri, Elena Fornari, Paolo Cavarzere, Claudia Piona, Massimiliano Corradi, Federica Emiliani, Alessandro Da Ros and 3 more

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In one paragraph

Article in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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4 · The record

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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

13 authors.

Claudio MaffeisDepartment of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy.
Anita MorandiDepartment of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy.ORCID 0000-0002-2631-9330
Chiara ZusiDepartment of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy.
Francesca OlivieriDepartment of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy.
Elena FornariDepartment of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy.
Paolo CavarzereDepartment of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy.
Claudia PionaDepartment of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy.ORCID 0000-0001-5168-8317
Massimiliano CorradiDepartment of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy.
Federica EmilianiDepartment of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy.
Alessandro Da RosPostgraduate School of Pediatrics, University of Verona, Verona, Italy.
Roberto Berni CananiDepartment of Translational Medical Science, University of Naples Federico II, Naples, Italy.
Alessandro MantovaniDepartment of Medicine, University of Verona, Verona, Italy.
Giovanni TargherDepartment of Medicine, University of Verona, Verona, Italy.ORCID 0000-0002-4325-3900

Funding

Università degli Studi di Verona (FURMAFF)
6 · The paper itself

Abstract

aimsFibroblast growth factor 21 (FGF21) decreases hepatic lipogenesis in animal models, and FGF21 analogues decrease serum triglycerides (TG) in adults in phase-2 trials. On the other hand, serum FGF21 is associated with higher TG in observational studies of people with obesity, raising a sort of paradox. We tested the hypothesis that FGF21 is induced by TG in youth with obesity, as a compensatory mechanism. MATERIALS AND

methodsWe recruited 159 children/adolescents with obesity (80 males, 12.7 ± 2.1 years). Besides serum FGF21 and lipid dosages, we genotyped the Pro446Leu variant at glucokinase regulator (GCKR) as a known marker of genetically increased hepatic de novo lipogenesis, and we used it as an instrumental variable to establish a cause-and-effect relationship between FGF21 and TG, according to a Mendelian randomization analysis.

resultsThe Pro446Leu variant increased circulating TG (β = +0.35, p < 0.001), which was positively associated with circulating FGF21 (β = +0.42, p < 0.001). The Pro446Leu variant increased FGF-21 (β = +0.14, p = 0.031) with the expected slope (β-coefficient) in case of association entirely mediated by TG: 0.35 (slope between Pro446Ala and TG) × 0.42 (slope between TG and FGF21) = 0.14.

conclusionsHepatic lipogenesis, marked by GCKR-modulated triglycerides, is significantly associated with increased serum FGF-21 in children/adolescents with obesity.

Indexed as

Adaptor Proteins, Signal TransducingFibroblast Growth FactorsLipogenesisLiverPediatric ObesityTriglyceridesAdolescentChildFemaleHumansMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideAdaptor Proteins, Signal TransducingFGF21 protein, humanfibroblast growth factor 21Fibroblast Growth FactorsGCKR protein, humanTriglyceridesinsulin resistancelipid‐lowering therapyliverobesity care

Identifiers

PMID39611214
PMCPMC11701186

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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 OpenQuestion graph.