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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Obesity

This article is part of the Research TopicThe Role of Adipose Tissue Dysfunction in the Pathogenesis of Obesity ComorbiditiesView all articles

Palmitic acid differently modulates extracellular vesicles and cellular fatty acid composition of SGBS adipocytes without impairing their insulin signalling

Provisionally accepted
Domenico  SergiDomenico Sergi1Sharon  AngeliniSharon Angelini1Fabiola  CastaldoFabiola Castaldo1Marco  BeccariaMarco Beccaria1Carlo  BellinghieriCarlo Bellinghieri1Flavio  FranchinaFlavio Franchina1Alice  OmenettoAlice Omenetto1Gabriella  StifaniGabriella Stifani1Sefora  Del MastroSefora Del Mastro1Stefania  MerighiStefania Merighi1Stefania  GessiStefania Gessi1Ravin  JugdaohsinghRavin Jugdaohsingh2Carlo  CervellatiCarlo Cervellati1Martin  WabitschMartin Wabitsch3Luca  Maria NeriLuca Maria Neri1Guillaume  BidaultGuillaume Bidault2Antonio  Vidal-PuigAntonio Vidal-Puig2Juana  Maria SanzJuana Maria Sanz1*Angelina  PassaroAngelina Passaro1
  • 1University of Ferrara, Ferrara, Italy
  • 2University of Cambridge, Cambridge, United Kingdom
  • 3Universitatsklinikum Ulm, Ulm, Germany

The final, formatted version of the article will be published soon.

Scope: Adipocyte-derived extracellular vesicle (EVs) lipid cargo reflects the obese metabolic state. Nevertheless, it is currently unknown whether adipocyte-derived EV lipid profile is influenced by saturated fatty acid overload. This study investigated if palmitic acid (PA) affected human Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte insulin sensitivity and the repercussions on the EV fatty acid cargo secreted by these cells. Methods: Adipocytes were treated with 500 μM or 1000 μM PA and cytotoxicity was assessed using the lactate dehydrogenase assay. Thereafter cells were treated with 1000 μM PA for 48h followed by the assessment of triglyceride accumulation and adipokine expression. Insulin signalling, NF-κβ activation and stearoyl-CoA desaturase-1 (SCD) abundance were assessed by Western blot. EVs were isolated via ultracentrifugation, intracellular as well as EV fatty acid profile characterised using gas-chromatography coupled to flame-ionization detector. Results: Both 500 μM or 1000 μM PA did not elicit a cytotoxic effect of SGBS adipocytes. PA promoted adipocyte hypertrophy without hampering insulin signalling nor triggering the activation of NF-κβ. However, PA increased intracellular and EV SFA content, raised intracellular oleic acid (OA) levels in parallel with the upregulation of SCD, while decreased OA content in EVs. Conclusions: Active lipid sorting within EVs may be an additional mechanisms underpinning intercellular communication by which adipocytes inform other cells about their metabolic status. However, further studies are warranted to evaluate the effects of EV lipid cargo on recipient cells.

Keywords: extracellular vesicles, Adipocytes, Palmitic Acid, Fatty Acids, Insulin Resistance

Received: 05 Sep 2025; Accepted: 04 Nov 2025.

Copyright: © 2025 Sergi, Angelini, Castaldo, Beccaria, Bellinghieri, Franchina, Omenetto, Stifani, Del Mastro, Merighi, Gessi, Jugdaohsingh, Cervellati, Wabitsch, Neri, Bidault, Vidal-Puig, Sanz and Passaro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Juana Maria Sanz, szj@unife.it

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