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

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.

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Publication Details

Journal
Nature Communications
Published
2026-04-11
DOI
https://doi.org/10.1038/s41467-026-71740-1
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Chun‐Kan Chen, Alex Larkin, Yun-Ling Pai, Toshiharu Onodera et al.
Nature Communications
Extracellular vesicles in disease
article

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

Chun‐Kan Chen, Alex Larkin, Yun-Ling Pai, Toshiharu Onodera, Jan‐Bernd Funcke, Christy Gliniak, Laurent Gautron, S Chen, Clair Crewe, Saket Awadhesbhai Patel, Philipp E. Scherer, Snigdha Tiash, May-Yun Wang, Marjori Russo, Yi-Cian Zheng
article en

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.

Nature Communications
Rutgers, The State University of New Jersey (US), Baylor College of Medicine (US), Washington University in St. Louis (US), Southwestern Medical Center (US), The University of Texas Southwestern Medical Center (US), The University of Osaka (JP)
American Heart Association, National Institutes of Health
Openalex Percentile: Top 21%
Extracellular vesicles in disease
DOIOpen Access PDFOpenAlex
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