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Precision medicine: toward restoring fat with gene therapy in inherited lipodystrophy

Gene Therapy (2024)Cite this article

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Inherited lipodystrophies belong to the heterogeneous group of syndromes characterized by a lack of adipose tissue (AT) associated with insulin resistance, hypertriglyceridemia, and Metabolic associated liver disease (MASLD) [1,2,3]. According to the severity and the anatomical distribution of AT, lipodystrophy could be generalized or partial [4]. Congenital generalized lipodystrophy (CGL) or Berardinelli-Seip congenital lipodystrophies (BSCL) are characterized by an extreme paucity of functional adipose tissue. Patients with BSCL develop insulin resistance and associated cardiometabolic abnormalities, soon after birth or in childhood. Familial partial lipodystrophies (FPLD) are characterized by a stereotypic pattern of AT loss affecting the limbs and normal or excess fat on the face and the neck [4]. Metabolic features range from asymptomatic impaired glucose tolerance with mild dyslipidaemia to severe insulin resistance, diabetes, and MASLD [5].

Lipodystrophies are genetically transmitted primary adipocyte dysfunctions, with each defective gene resulting in a distinct AT loss mechanism [6]. As a result, therapeutic management of lipodystrophies is extremely difficult because the organ that should be addressed is virtually missing, and decoding the mechanism necessitates a thorough understanding of the biological role of each gene involved. Furthermore, cardiometabolic problems are generally difficult to manage and have a significant impact on both quality of life and life expectancy [7].

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Authors and Affiliations

  1. l’Institut du Thorax, INSERM, CNRS, Nantes Université, CHU Nantes, Nantes, France

    Xavier Prieur

  2. Department of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, USA

    Lei Cao

  3. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Lei Cao

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  1. Xavier Prieur
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XP and LC wrote the manuscript.

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Correspondence to Xavier Prieur or Lei Cao.

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Prieur, X., Cao, L. Precision medicine: toward restoring fat with gene therapy in inherited lipodystrophy. Gene Ther (2024). https://doi.org/10.1038/s41434-024-00489-3

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