MAGI'S LAB, Rovereto (TN), Italy.
Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):249-255. doi: 10.7417/CT.2023.2495.
Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease.
This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction.
Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones.
The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals.
尽管脂肪代谢障碍对患者的生活质量有重大影响，但它仍是一种复杂且神秘的脂肪组织疾病，目前仍未被充分了解。遗传研究揭示了其发病机制的潜在因素，包括体细胞突变，这是非遗传性的遗传改变，在这种疾病的发展中起着关键作用。
本综述旨在通过研究体细胞突变对脂肪组织生物学、炎症和代谢功能障碍的影响，阐明其在脂肪代谢障碍发病机制中的作用。
研究集中在白细胞克隆、TET2 和 DNMT3A 等遗传改变，以及脂肪组织与其他器官之间的复杂相互作用，揭示了驱动脂肪代谢障碍的潜在机制。从对科学文献的研究中，可以看出与三个主要途径相关的基因突变可能与脂肪代谢障碍的体细胞发展有关：与线粒体活性相关的基因、与皮下脂肪组织局部紊乱相关的基因和白细胞克隆的基因。
这些不同研究的结果表明，脂肪代谢障碍存在复杂的遗传基础，并为针对体细胞突变的治疗干预提供了潜在途径，以减轻受影响个体的疾病负担。
