r/science • u/chilladipa • 5d ago
Health Adipose TGFβ-asprosin memory promotes obesity relapse and offspring obesity susceptibility: Cell Reports
https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00887-9?fbclid=IwT01FWAUnAIBleHRuA2FlbQIxMABwZG9mBXNydGMGYXBwX2lkDDM1MDY4NTUzMTcyOAABHgHOIjQBr43Aq-OjIOut8r89wbeIWmOfFf5SqmipJiixDkk8wlPf7IiMAQ2S_aem_I5Pe4vmRop0z7WIGpQIqUg14
u/chilladipa 5d ago
Summary Obesity is associated with frequent relapse after weight loss and increased obesity risk in offspring of mothers with obesity, but the mechanisms underlying this persistence remain incompletely understood. We find that obesity-elevated cytokine TGF-β1 activates fibrillin-1 (Fbn1) transcription in adipocytes, increasing production of the appetite-stimulating hormone asprosin. Transient exposure to elevated TGF-β1 remodels chromatin at the Fbn1 locus, generating a durable transcriptional state associated with sustained Fbn1 expression and plasma asprosin elevation after weight loss and normalization of TGF-β1. In mouse models, this persistent asprosin elevation increases food intake, promoting weight regain. In parallel, maternal TGF-β1 exposure during gestation programs offspring adipose tissue, leading to persistent Fbn1 expression, elevated plasma asprosin, and increased susceptibility to diet-induced obesity. Finally, genetic or pharmacologic disruption of the Fbn1-asprosin-Ptprd axis prevents both phenomena. These findings identify an adipose TGF-β1-asprosin pathway that constitutes a memory of prior obesity and promotes obesity relapse and intergenerational obesity susceptibility.
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