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FPLD2 is caused by pathogenic variants in the\n                    <jats:italic>LMNA<\/jats:italic>\n                    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 8 families with developing or established FPLD2 and performed clinical, histological, and transcriptomic analyses of subcutaneous adipose tissue biopsies. Bulk and single-nucleus RNA sequencing revealed suppression of lipid metabolism and mitochondrial pathways, alongside increased inflammation. These signatures were mirrored in tamoxifen-inducible adipocyte-specific\n                    <jats:italic>Lmna<\/jats:italic>\n                    -knockout mice, in which lamin A\/C-deficient adipocytes shrank and disappeared.\n                    <jats:italic>Lmna-<\/jats:italic>\n                    deficient fibroblasts shared similar gene expression changes, linked to altered chromatin accessibility, underscoring lamin A\/C\u2019s potential regulatory role in lipid metabolism and inflammatory programs. By directly comparing atrophic and hypertrophic adipose depots in FPLD2, and integrating human, mouse, and in vitro models, this study provides insights into disease progression and potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1172\/jci198387","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T17:00:37Z","timestamp":1762880437000},"source":"Crossref","is-referenced-by-count":4,"title":["Altered lipid metabolism and inflammatory programs associate with adipocyte loss in familial partial lipodystrophy 2"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-0614","authenticated-orcid":true,"given":"Jessica N.","family":"Maung","sequence":"first","affiliation":[{"name":"Department of Molecular & Integrative Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Schill","sequence":"additional","affiliation":[{"name":"Department of Molecular & 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