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REVIEW article
Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 |
doi: 10.3389/fendo.2024.1394102
This article is part of the Research Topic Improving Diagnosis and Management of Genetic Lipodystrophy View all 5 articles
Familial partial lipodystrophy resulting from loss-of-function PPARγ pathogenic variants: phenotypic, clinical, and genetic features
Provisionally accepted- Federal University of Rio Grande do Norte, Natal, Brazil
The PPARG gene encodes a member of a nuclear receptor superfamily known as peroxisome proliferator-activated gamma (PPARγ). PPARγ plays an essential role in adipogenesis, stimulating the differentiation of preadipocytes into adipocytes. Loss-of-function pathogenic variants in PPARG reduce the activity of the PPARγ receptor and can lead to severe metabolic consequences associated with familial partial lipodystrophy type 3 (FPLD3). This review focuses on recent scientific data related to FPLD3, including the role of PPARγ in adipose tissue metabolism and the phenotypic and clinical consequences of loss-of-function variants in the PPARG gene. The clinical features of 41 PPARG pathogenic variants associated with FPLD3 patients were reviewed, highlighting the genetic and clinical heterogeneity observed among 91 patients. Most of them were female, and the average age at the onset and diagnosis of lipoatrophy was 21 years and 33 years, respectively. Considering the metabolic profile, hypertriglyceridemia (91.9% of cases), diabetes (77%), hypertension (59.5%), polycystic ovary syndrome (58.2% of women), and metabolic-dysfunction-associated fatty liver disease (87,5%). We also discuss the current treatment for FPLD3. This review provides new data concerning the genetic and clinical heterogeneity in FPLD3 and highlights the importance of further understanding the genetics of this rare disease.
Keywords: PPAR gamma, Adipose Tissue, genetic lipodystrophy, Insulin Resistance, Diabetes Mellitus
Received: 01 Mar 2024; Accepted: 10 Sep 2024.
Copyright: © 2024 Soares, da Silva, Campos and Lima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Reivla M. Soares, Federal University of Rio Grande do Norte, Natal, Brazil
Josivan G. Lima, Federal University of Rio Grande do Norte, Natal, Brazil
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