Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects

E. Petrangeli, G. Coroniti, Anna Teresa Brini, Laura De Girolamo, Deborah Stanco, Stefania Niada, G. Silecchia, Emanuela Morgante, C. Lubrano, Matteo Antonio Russo, Luisa Salvatori

Research output: Contribution to journalArticle

Abstract

Low-grade chronic inflammation is a salient feature of obesity and many associated disorders. This condition frequently occurs in central obesity and is connected to alterations of the visceral adipose tissue (AT) microenvironment. Understanding how obesity is related to inflammation may allow the development of therapeutics aimed at improving metabolic parameters in obese patients. To achieve this aim, we compared the features of two subpopulations of adipose-derived stem cells (ASC) isolated from both subcutaneous and visceral AT of obese patients with the features of two subpopulations of ASC from the same isolation sites of non-obese individuals. In particular, the behavior of ASC of obese versus non-obese subjects during hypoxia, which occurs in obese AT and is an inducer of the inflammatory response, was evaluated. Obesity deeply influenced ASC from visceral AT (obV-ASC); these cells appeared to exhibit clearly distinguishable morphology and ultrastructure as well as reduced proliferation, clonogenicity and expression of stemness, differentiation and inflammation-related genes. These cells also exhibited a deregulated response to hypoxia, which induced strong tissue-specific NF-kB activation and an NF-kB-mediated increase in inflammatory and fibrogenic responses. Moreover, obV-ASC, which showed a less stem-like phenotype, recovered stemness features after hypoxia. Our findings demonstrated the peculiar behavior of obV-ASC, their influence on the obese visceral AT microenvironment and the therapeutic potential of NF-kB inhibitors. These novel findings suggest that the deregulated hyper-responsiveness to hypoxic stimulus of ASC from visceral AT of obese subjects may contribute via paracrine mechanisms to low-grade chronic inflammation, which has been implicated in obesity-related morbidity.

Original languageEnglish
Pages (from-to)668-679
Number of pages12
JournalJournal of Cellular Physiology
Volume231
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Intra-Abdominal Fat
Stem cells
Adipocytes
Stem Cells
Fats
Tissue
NF-kappa B
Obesity
Inflammation
Abdominal Obesity
Hypoxia
Cell Separation
Subcutaneous Fat
Adipose Tissue
Genes
Chemical activation
Morbidity
Phenotype
Therapeutics

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects. / Petrangeli, E.; Coroniti, G.; Brini, Anna Teresa; De Girolamo, Laura; Stanco, Deborah; Niada, Stefania; Silecchia, G.; Morgante, Emanuela; Lubrano, C.; Russo, Matteo Antonio; Salvatori, Luisa.

In: Journal of Cellular Physiology, Vol. 231, No. 3, 01.03.2016, p. 668-679.

Research output: Contribution to journalArticle

Petrangeli, E, Coroniti, G, Brini, AT, De Girolamo, L, Stanco, D, Niada, S, Silecchia, G, Morgante, E, Lubrano, C, Russo, MA & Salvatori, L 2016, 'Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects', Journal of Cellular Physiology, vol. 231, no. 3, pp. 668-679. https://doi.org/10.1002/jcp.25113
Petrangeli, E. ; Coroniti, G. ; Brini, Anna Teresa ; De Girolamo, Laura ; Stanco, Deborah ; Niada, Stefania ; Silecchia, G. ; Morgante, Emanuela ; Lubrano, C. ; Russo, Matteo Antonio ; Salvatori, Luisa. / Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects. In: Journal of Cellular Physiology. 2016 ; Vol. 231, No. 3. pp. 668-679.
@article{3960d8342b97416e877106178cd0feb1,
title = "Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects",
abstract = "Low-grade chronic inflammation is a salient feature of obesity and many associated disorders. This condition frequently occurs in central obesity and is connected to alterations of the visceral adipose tissue (AT) microenvironment. Understanding how obesity is related to inflammation may allow the development of therapeutics aimed at improving metabolic parameters in obese patients. To achieve this aim, we compared the features of two subpopulations of adipose-derived stem cells (ASC) isolated from both subcutaneous and visceral AT of obese patients with the features of two subpopulations of ASC from the same isolation sites of non-obese individuals. In particular, the behavior of ASC of obese versus non-obese subjects during hypoxia, which occurs in obese AT and is an inducer of the inflammatory response, was evaluated. Obesity deeply influenced ASC from visceral AT (obV-ASC); these cells appeared to exhibit clearly distinguishable morphology and ultrastructure as well as reduced proliferation, clonogenicity and expression of stemness, differentiation and inflammation-related genes. These cells also exhibited a deregulated response to hypoxia, which induced strong tissue-specific NF-kB activation and an NF-kB-mediated increase in inflammatory and fibrogenic responses. Moreover, obV-ASC, which showed a less stem-like phenotype, recovered stemness features after hypoxia. Our findings demonstrated the peculiar behavior of obV-ASC, their influence on the obese visceral AT microenvironment and the therapeutic potential of NF-kB inhibitors. These novel findings suggest that the deregulated hyper-responsiveness to hypoxic stimulus of ASC from visceral AT of obese subjects may contribute via paracrine mechanisms to low-grade chronic inflammation, which has been implicated in obesity-related morbidity.",
author = "E. Petrangeli and G. Coroniti and Brini, {Anna Teresa} and {De Girolamo}, Laura and Deborah Stanco and Stefania Niada and G. Silecchia and Emanuela Morgante and C. Lubrano and Russo, {Matteo Antonio} and Luisa Salvatori",
year = "2016",
month = "3",
day = "1",
doi = "10.1002/jcp.25113",
language = "English",
volume = "231",
pages = "668--679",
journal = "Journal of cellular and comparative physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects

AU - Petrangeli, E.

AU - Coroniti, G.

AU - Brini, Anna Teresa

AU - De Girolamo, Laura

AU - Stanco, Deborah

AU - Niada, Stefania

AU - Silecchia, G.

AU - Morgante, Emanuela

AU - Lubrano, C.

AU - Russo, Matteo Antonio

AU - Salvatori, Luisa

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Low-grade chronic inflammation is a salient feature of obesity and many associated disorders. This condition frequently occurs in central obesity and is connected to alterations of the visceral adipose tissue (AT) microenvironment. Understanding how obesity is related to inflammation may allow the development of therapeutics aimed at improving metabolic parameters in obese patients. To achieve this aim, we compared the features of two subpopulations of adipose-derived stem cells (ASC) isolated from both subcutaneous and visceral AT of obese patients with the features of two subpopulations of ASC from the same isolation sites of non-obese individuals. In particular, the behavior of ASC of obese versus non-obese subjects during hypoxia, which occurs in obese AT and is an inducer of the inflammatory response, was evaluated. Obesity deeply influenced ASC from visceral AT (obV-ASC); these cells appeared to exhibit clearly distinguishable morphology and ultrastructure as well as reduced proliferation, clonogenicity and expression of stemness, differentiation and inflammation-related genes. These cells also exhibited a deregulated response to hypoxia, which induced strong tissue-specific NF-kB activation and an NF-kB-mediated increase in inflammatory and fibrogenic responses. Moreover, obV-ASC, which showed a less stem-like phenotype, recovered stemness features after hypoxia. Our findings demonstrated the peculiar behavior of obV-ASC, their influence on the obese visceral AT microenvironment and the therapeutic potential of NF-kB inhibitors. These novel findings suggest that the deregulated hyper-responsiveness to hypoxic stimulus of ASC from visceral AT of obese subjects may contribute via paracrine mechanisms to low-grade chronic inflammation, which has been implicated in obesity-related morbidity.

AB - Low-grade chronic inflammation is a salient feature of obesity and many associated disorders. This condition frequently occurs in central obesity and is connected to alterations of the visceral adipose tissue (AT) microenvironment. Understanding how obesity is related to inflammation may allow the development of therapeutics aimed at improving metabolic parameters in obese patients. To achieve this aim, we compared the features of two subpopulations of adipose-derived stem cells (ASC) isolated from both subcutaneous and visceral AT of obese patients with the features of two subpopulations of ASC from the same isolation sites of non-obese individuals. In particular, the behavior of ASC of obese versus non-obese subjects during hypoxia, which occurs in obese AT and is an inducer of the inflammatory response, was evaluated. Obesity deeply influenced ASC from visceral AT (obV-ASC); these cells appeared to exhibit clearly distinguishable morphology and ultrastructure as well as reduced proliferation, clonogenicity and expression of stemness, differentiation and inflammation-related genes. These cells also exhibited a deregulated response to hypoxia, which induced strong tissue-specific NF-kB activation and an NF-kB-mediated increase in inflammatory and fibrogenic responses. Moreover, obV-ASC, which showed a less stem-like phenotype, recovered stemness features after hypoxia. Our findings demonstrated the peculiar behavior of obV-ASC, their influence on the obese visceral AT microenvironment and the therapeutic potential of NF-kB inhibitors. These novel findings suggest that the deregulated hyper-responsiveness to hypoxic stimulus of ASC from visceral AT of obese subjects may contribute via paracrine mechanisms to low-grade chronic inflammation, which has been implicated in obesity-related morbidity.

UR - http://www.scopus.com/inward/record.url?scp=84949008086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949008086&partnerID=8YFLogxK

U2 - 10.1002/jcp.25113

DO - 10.1002/jcp.25113

M3 - Article

VL - 231

SP - 668

EP - 679

JO - Journal of cellular and comparative physiology

JF - Journal of cellular and comparative physiology

SN - 0021-9541

IS - 3

ER -