Whole-exome and genome sequencing in consanguineous families with unsolved lipodystrophy identified biallelic pathogenic loss-of-function variants in the phospholipase gene PLAAT3. Multi-omics and functional analyses in human and mouse PLAAT3-deficient adipose tissue and adipose stem cells revealed an adipocyte differentiation defect that is mediated by an altered gene network downstream of the adipogenesis master regulator PPARγ.
References
Mann, J. P. & Savage, D. B. What lipodystrophies teach us about the metabolic syndrome. J. Clin. Invest. 129, 4009–4021 (2019). A review that clearly explains the general interest of studying genetic lipodystrophies to understand the metabolic syndrome.
Jaworski, K. et al. AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat. Med. 15, 159–169 (2009). This paper reports a Plaat3-knockout mouse that shows features of a lipodystrophy syndrome.
Qin, Q. et al. Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data. Genome Biol. 21, 32 (2020). This paper describes a user-friendly bioinformatics tool to predict the transcriptional regulators of differentially expressed gene sets.
Ahmadian, M. et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat. Med. 19, 557–566 (2013). A review that discusses the pros and cons of PPARγ agonists as potent insulin sensitizers in the treatment of type 2 diabetes.
Sobreira, N. et al. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum. Mut. 36, 928–930 (2015). This paper describes a freely accessible web-based tool to identify additional individuals with rare phenotypes and variants in a gene of interest.
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This is a summary of: Schuermans, N. et al. Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPAR signaling. Nat. Genet. https://doi.org/10.1038/s41588-023-01535-3 (2023).
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Phospholipid modifier PLAAT3 links defective PPARγ-dependent signaling to lipodystrophy. Nat Genet 55, 1790–1791 (2023). https://doi.org/10.1038/s41588-023-01536-2
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DOI: https://doi.org/10.1038/s41588-023-01536-2
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