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Unravelling leptin variants: advancing precision medicine in obesity

Nature Reviews Endocrinology volume 19, pages 562–563 (2023)Cite this article

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Funcke et al. shed light on the management of leptin replacement therapy in monogenic obesity by identifying two LEP variants with antagonistic functional effects. Their groundbreaking study emphasizes the urgent need for in-depth understanding of the genetic factors involved in obesity to pave the way for tailored interventions.

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References

  1. Farooqi, I. S. Monogenic human obesity syndromes. Handb. Clin. Neurol. 181, 301–310 (2021).

    Article  PubMed  Google Scholar 

  2. Courbage, S. et al. Implication of heterozygous variants in genes of the leptin-melanocortin pathway in severe obesity. J. Clin. Endocrinol. Metab. 106, 2991–3006 (2021).

    Article  PubMed  Google Scholar 

  3. Clément, K. et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 8, 960–970 (2020).

    Article  PubMed  Google Scholar 

  4. Funcke, J.-B. et al. Monogenic forms of childhood obesity due to mutations in the leptin gene. Mol. Cell. Pediatr. 1, 3 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fischer-Posovszky, P., Funcke, J.-B. & Wabitsch, M. Biologically inactive leptin and early-onset extreme obesity. N. Engl. J. Med. 372, 1266–1267 (2015).

    Article  PubMed  Google Scholar 

  6. Funcke, J.-B. et al. Rare antagonistic leptin variants and severe, early-onset obesity. N. Engl. J. Med. 388, 2253–2261 (2023).

    Article  CAS  PubMed  Google Scholar 

  7. Wabitsch, M. et al. Severe early-onset obesity due to bioinactive leptin caused by a p.N103K mutation in the leptin gene. J. Clin. Endocrinol. Metab. 100, 3227–3230 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Weghuber, D. et al. Once-weekly semaglutide in adolescents with obesity. N. Engl. J. Med. 387, 2245–2257 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Assistance Publique-Hôpitaux de Paris, French Reference Center for Prader-Willi Syndrome and other rare obesities (PRADORT), Paris, France

    Béatrice Dubern & Karine Clément

  2. Nutrition and Obesities: Systemic Approaches Research Unit (Nutriomics), Sorbonne Université, INSERM, Paris, France

    Béatrice Dubern & Karine Clément

Authors
  1. Béatrice Dubern
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  2. Karine Clément
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Correspondence to Béatrice Dubern.

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The authors declare no competing interests.

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Cite this article

Dubern, B., Clément, K. Unravelling leptin variants: advancing precision medicine in obesity. Nat Rev Endocrinol 19, 562–563 (2023). https://doi.org/10.1038/s41574-023-00882-9

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