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The Interplay of UCP3 and PCSK1 Variants in Severe Obesity.

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Τίτλος: The Interplay of UCP3 and PCSK1 Variants in Severe Obesity.
Συγγραφείς: Verde L; Department of Public Health, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.; Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA., Galasso M; Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy., Coletta DK; Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.; Department of Physiology, University of Arizona, Tucson, AZ, USA.; Center for Disparities in Diabetes, Obesity and Metabolism, University of Arizona, Tucson, AZ, USA., Savastano S; Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.; Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy., Mandarino LJ; Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.; Center for Disparities in Diabetes, Obesity and Metabolism, University of Arizona, Tucson, AZ, USA., Colao A; Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.; Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.; Cattedra Unesco 'Educazione Alla Salute E Allo Sviluppo Sostenibile', University Federico II, 80131, Naples, Italy., Barrea L; Dipartimento di Psicologia e Scienze della Salute, , Università Telematica Pegaso, Centro Direzionale Isola F2, Via Porzio, Isola F2, 80143, Naples, Italy., Muscogiuri G; Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA. giovanna.muscogiuri@unina.it.; Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy. giovanna.muscogiuri@unina.it.; Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy. giovanna.muscogiuri@unina.it.; Cattedra Unesco 'Educazione Alla Salute E Allo Sviluppo Sostenibile', University Federico II, 80131, Naples, Italy. giovanna.muscogiuri@unina.it.
Πηγή: Current obesity reports [Curr Obes Rep] 2025 Apr 26; Vol. 14 (1), pp. 38. Date of Electronic Publication: 2025 Apr 26.
Τύπος έκδοσης: Journal Article; Review; Case Reports
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Current Medicine Group Country of Publication: United States NLM ID: 101578283 Publication Model: Electronic Cited Medium: Internet ISSN: 2162-4968 (Electronic) Linking ISSN: 21624968 NLM ISO Abbreviation: Curr Obes Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: [Philadelphia, PA] : Current Medicine Group
Ιατρικοί όροι (MeSH): Uncoupling Protein 3*/genetics , Uncoupling Protein 3*/metabolism , Obesity, Morbid*/genetics , Obesity, Morbid*/metabolism , Proprotein Convertase 1*/genetics , Proprotein Convertase 1*/metabolism, Insulin Resistance/genetics ; Humans ; Female ; Male ; Genetic Predisposition to Disease ; Adult
Περίληψη: Obesity is a heterogeneous and multifactorial disease with a strong genetic component. While polygenic obesity accounts for most common cases, rare monogenic variants contribute, particularly in severe, early-onset obesity. Among the lesser-studied candidates are UCP3 and PCSK1, genes involved in key metabolic pathways. RECENT FINDINGS: The UCP3 p.Val192Ile (c.574G > A) and PCSK1 p.Asn221Asp (c.661 A > G) variants have been independently associated with metabolic pathways, including fatty acid oxidation and hormone processing, as well as a modestly increased risk of obesity. Clinical and genetic characterization of two patients with severe early-onset obesity revealed the co-occurrence of these variants, which were associated with metabolic disturbances such as insulin resistance. PURPOSE OF THE REVIEW: This narrative review examined the functional and clinical significance of UCP3 and PCSK1 variants in severe obesity, presenting two case reports to illustrate their potential impact. Our findings support a potential model in which rare variants in distinct metabolic genes may interact synergistically to exacerbate disease severity. Further studies are needed to elucidate their combined functional effects and contributions to obesity pathogenesis.
(© 2025. The Author(s).)
Competing Interests: Declarations. Competing Interests: The authors declare no competing interests.
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Substance Nomenclature: 0 (Uncoupling Protein 3)
0 (UCP3 protein, human)
EC 3.4.21.93 (Proprotein Convertase 1)
EC 3.4.21.93 (PCSK1 protein, human)
Entry Date(s): Date Created: 20250425 Date Completed: 20250426 Latest Revision: 20250502
Update Code: 20260130
PubMed Central ID: PMC12031958
DOI: 10.1007/s13679-025-00631-1
PMID: 40281302
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2162-4968
DOI:10.1007/s13679-025-00631-1