Lamin A/C regulates lipid metabolism and inflammation: insights from models of familial partial lipodystrophy 2.

ABSTRACT: Familial partial lipodystrophy 2 (FPLD2) is a rare disease characterized by adipose tissue loss and redistribution, and metabolic dysfunction. FPLD2 is caused by pathogenic variants in the LMNA gene, encoding nuclear lamins A/C, structural proteins that control nuclear function and gene expression. However, the mechanisms driving adipocyte loss in FPLD2 remain poorly defined. In this study, we recruited eight families with developing or established FPLD2 and performed clinical, histological, and transcriptomic analyses of subcutaneous adipose tissue biopsies. Bulk and single-nuclei RNA-sequencing revealed suppression of lipid metabolism and mitochondrial pathways, alongside increased inflammation. These signatures were mirrored in tamoxifen-inducible adipocyte-specific Lmna knockout mice,

SUBMITTER: Maung JN 

PROVIDER: S-EPMC12721891 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature