Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells

Sabena M. Conley, Xiang Yang Zhu, Alfonso Eirin, Hui Tang, Amir Lerman, Andre J van Wijnen, Lilach O Lerman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aims: Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Methods: Domestic pigs consumed a lean or obese diet (n = 6 each) for 16. weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change. >. 1.4, p <. 0.05) and suppressed (fold change. <. 0.7, p <. 0.05) mRNAs in MetS pigs were functionally interpreted by gene ontology analysis. The most prominently upregulated and downregulated mRNAs were further probed. Results: We identified in MetS-MSC 168 up-regulated and 51 down-regulated mRNAs related to insulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. Conclusions: MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS.

Original languageEnglish (US)
JournalGene
DOIs
StateAccepted/In press - 2017

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Mesenchymal Stromal Cells
Swine
Insulin
Genes
Messenger RNA
Insulin Resistance
Adipose Tissue
Adipocytes
Abdominal Subcutaneous Fat
Glucose
High-Throughput Nucleotide Sequencing
Sus scrofa
Gene Ontology
Calcium Signaling
Chronic Renal Insufficiency

Keywords

  • Insulin
  • Mesenchymal stem cells
  • Metabolic syndrome
  • MRNA

ASJC Scopus subject areas

  • Genetics

Cite this

Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells. / Conley, Sabena M.; Zhu, Xiang Yang; Eirin, Alfonso; Tang, Hui; Lerman, Amir; van Wijnen, Andre J; Lerman, Lilach O.

In: Gene, 2017.

Research output: Contribution to journalArticle

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abstract = "Aims: Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Methods: Domestic pigs consumed a lean or obese diet (n = 6 each) for 16. weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change. >. 1.4, p <. 0.05) and suppressed (fold change. <. 0.7, p <. 0.05) mRNAs in MetS pigs were functionally interpreted by gene ontology analysis. The most prominently upregulated and downregulated mRNAs were further probed. Results: We identified in MetS-MSC 168 up-regulated and 51 down-regulated mRNAs related to insulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. Conclusions: MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS.",
keywords = "Insulin, Mesenchymal stem cells, Metabolic syndrome, MRNA",
author = "Conley, {Sabena M.} and Zhu, {Xiang Yang} and Alfonso Eirin and Hui Tang and Amir Lerman and {van Wijnen}, {Andre J} and Lerman, {Lilach O}",
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AU - Conley, Sabena M.

AU - Zhu, Xiang Yang

AU - Eirin, Alfonso

AU - Tang, Hui

AU - Lerman, Amir

AU - van Wijnen, Andre J

AU - Lerman, Lilach O

PY - 2017

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N2 - Aims: Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Methods: Domestic pigs consumed a lean or obese diet (n = 6 each) for 16. weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change. >. 1.4, p <. 0.05) and suppressed (fold change. <. 0.7, p <. 0.05) mRNAs in MetS pigs were functionally interpreted by gene ontology analysis. The most prominently upregulated and downregulated mRNAs were further probed. Results: We identified in MetS-MSC 168 up-regulated and 51 down-regulated mRNAs related to insulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. Conclusions: MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS.

AB - Aims: Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Methods: Domestic pigs consumed a lean or obese diet (n = 6 each) for 16. weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change. >. 1.4, p <. 0.05) and suppressed (fold change. <. 0.7, p <. 0.05) mRNAs in MetS pigs were functionally interpreted by gene ontology analysis. The most prominently upregulated and downregulated mRNAs were further probed. Results: We identified in MetS-MSC 168 up-regulated and 51 down-regulated mRNAs related to insulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. Conclusions: MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS.

KW - Insulin

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KW - MRNA

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