Longevity & Aging

Lamin A/C Loss Silences Fat Metabolism and Fuels Inflammation in Rare Lipodystrophy

Familial partial lipodystrophy type 2 (FPLD2) is a rare disease caused by LMNA variants. It makes people lose fat from the limbs and trunk, accumulate it in the neck, face and viscera, and develop metabolic problems. Researchers studied 8 families, taking abdominal and upper-neck fat biopsies and running bulk and single-nucleus RNA sequencing. Fat tissue from people with FPLD2 showed reduced activity of fatty acid metabolism, mitochondrial and translation pathways, and increased inflammatory, intermediate filament and muscle-related signatures. Similar changes appeared in a new tamoxifen-inducible adipocyte-specific Lmna-knockout mouse, where adipocytes shrank and disappeared, and in Lmna-deficient fibroblasts with altered chromatin accessibility. The work suggests lamin A/C helps maintain adipocytes by regulating lipid and immune gene programs, pointing to possible therapeutic targets. The cohort is small and the findings are largely descriptive.