Adipocytes signal to recruit specific mRNAs from surrounding cells to restore expression deficits.

Crewe, Clair; Gliniak, Christy M; Onodera, Toshiharu; Chen, Shiuhwei; Funcke, Jan-Bernd; Wang, May-Yun; Tiash, Snigdha; Pai, Yun-Ling et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

Extracellular vesicles (EVs) are nano-sized, membrane-delimited, particles released by cells that carry signaling macromolecules. A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discover that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA. This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results point to a selective mechanism by which specific mRNA molecules are acquired from the microenvironment to a level that can restore expression of mRNA and protein in a cell that is depleted of the corresponding genetic information.