Perilipin 2 modulates adipogenic differentiation of primary dermal fibroblasts and is extracellularly released during adipocyte maturation
5 affiliations
- 1Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- 2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- 3CNR National Research Council of Italy, IAC Institute for Applied Computing, Rome, Italy
- 4Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy
- 5Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
Abstract
Perilipin 2 (PLIN2) is a lipid droplet (LD)-associated protein broadly expressed across tissues, where it regulates fatty acid uptake, lipid storage, and LD dynamics. During adipogenesis, PLIN2 is localized to small LDs in preadipocytes but is absent in mature adipocytes, where it is replaced by other perilipins. Whether PLIN2 loss represents a driver or a consequence of adipogenic differentiation remains unresolved. To address this question, we performed in vitro and ex vivo analyses. Adipogenic differentiation was induced in human primary dermal fibroblasts (DFs), and PLIN2 function was investigated using small interfering RNA (siRNA)-mediated silencing and treatment with Brefeldin A and Monensin (B + M). In parallel, plasma samples from both physically active healthy subjects and patients with mobility impairment were analyzed to assess PLIN2 expression. PLIN2 silencing accelerated adipogenic differentiation, whereas its higher expression induced by B + M markedly delayed this process. Notably, although Plin2 mRNA became nearly undetectable during differentiation, PLIN2 protein continued to be synthesized and, at variance with DFs, released into the culture supernatant as a circulating form (cPLIN2), partially associated with extracellular vesicles. Consistent with these findings, plasma cPLIN2 levels in vivo positively correlated with increased adiposity and low physical activity. Moreover, skeletal muscle samples from healthy subjects exhibited higher expression of CD36, a recently identified PLIN2 interactor, compared with patients. Collectively, these data identify PLIN2 as a negative regulator of the early phases of adipogenic differentiation and suggest that its secretion may represent a mechanism of interorgan communication potentially mediated by extracellular vesicles.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06358-z.
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BibTeX
@article{conte2026perilipin,
title = {{Perilipin 2 modulates adipogenic differentiation of primary dermal fibroblasts and is extracellularly released during adipocyte maturation}},
author = {Maria Conte and Lorenzo Trofarello and Antonio Chiariello and Gianluca Storci and Paolo Tieri and Giuseppe Conte and Margherita Cortini and Sofia Avnet and Nicola Baldini and Gianandrea Pasquinelli and Sabrina Valente and Stefano Salvioli},
journal = {Cellular and Molecular Life Sciences: CMLS},
year = {2026},
month = jul,
doi = {10.1007/s00018-026-06358-z},
url = {https://doi.org/10.1007/s00018-026-06358-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Perilipin 2 modulates adipogenic differentiation of primary dermal fibroblasts and is extracellularly released during adipocyte maturation
AU - Maria Conte
AU - Lorenzo Trofarello
AU - Antonio Chiariello
AU - Gianluca Storci
AU - Paolo Tieri
AU - Giuseppe Conte
AU - Margherita Cortini
AU - Sofia Avnet
AU - Nicola Baldini
AU - Gianandrea Pasquinelli
AU - Sabrina Valente
AU - Stefano Salvioli
PY - 2026
DA - 2026/07/28
JO - Cellular and Molecular Life Sciences: CMLS
DO - 10.1007/s00018-026-06358-z
UR - https://doi.org/10.1007/s00018-026-06358-z
AB - Perilipin 2 (PLIN2) is a lipid droplet (LD)-associated protein broadly expressed across tissues, where it regulates fatty acid uptake, lipid storage, and LD dynamics. During adipogenesis, PLIN2 is localized to small LDs in preadipocytes but is absent in mature adipocytes, where it is replaced by other perilipins. Whether PLIN2 loss represents a driver or a consequence of adipogenic differentiation remains unresolved. To address this question, we performed in vitro and ex vivo analyses. Adipogenic differentiation was induced in human primary dermal fibroblasts (DFs), and PLIN2 function was investigated using small interfering RNA (siRNA)-mediated silencing and treatment with Brefeldin A and Monensin (B + M). In parallel, plasma samples from both physically active healthy subjects and patients with mobility impairment were analyzed to assess PLIN2 expression. PLIN2 silencing accelerated adipogenic differentiation, whereas its higher expression induced by B + M markedly delayed this process. Notably, although Plin2 mRNA became nearly undetectable during differentiation, PLIN2 protein continued to be synthesized and, at variance with DFs, released into the culture supernatant as a circulating form (cPLIN2), partially associated with extracellular vesicles. Consistent with these findings, plasma cPLIN2 levels in vivo positively correlated with increased adiposity and low physical activity. Moreover, skeletal muscle samples from healthy subjects exhibited higher expression of CD36, a recently identified PLIN2 interactor, compared with patients. Collectively, these data identify PLIN2 as a negative regulator of the early phases of adipogenic differentiation and suggest that its secretion may represent a mechanism of interorgan communication potentially mediated by extracellular vesicles. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06358-z.
SN - 1420-682X
SN - 1420-9071
ER -