Obesity-induced mitochondrial dysfunction in porcine adipose tissue-derived mesenchymal stem cells

Yu Meng, Alfonso Eirin, Xiang Yang Zhu, Hui Tang, Pritha Chanana, Amir Lerman, Andre J. van Wijnen, Lilach O. Lerman

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Transplantation of autologous mesenchymal stem cells (MSCs) may be a viable option for treatment of several diseases. MSCs efficacy depends on adequate function of their mitochondria, which might be impaired in a noxious milieu. We hypothesized that obesity compromises MSCs mitochondrial structure and function, possibly via micro-RNA (miRNA)-based mechanisms. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet (n = 7 each). Mitochondrial structure was assessed by electron microscopy and function by membrane potential and cytochrome-c oxidase (COX)-IV activity. Oxidative stress was assessed by Mito-SOX and dihydroethidium staining. Next-generation sequencing (RNA-seq) was performed to identify miRNAs expression in MSCs, and predicted mitochondrial target genes were then identified (MitoCarta). Compared to Lean-MSCs, mitochondria from Obese-MSCs were smaller and showed cristae remodeling and loss. Mitochondrial membrane potential and COX-IV activity decreased in Obese-MSCs, associated with increased mitochondrial oxidative stress. RNA-seq generated reads for 413 miRNAs, of which 5 miRNAs were upregulated in Obese-MSCs (fold change >2, p < 0.05) and found to target 43 specific mitochondrial genes. Obesity impairs MSC mitochondrial structure and function, possibly mediated partly through miRNA-induced mitochondrial gene regulation, leading to increased oxidative stress. Importantly, these alterations may limit the therapeutic use of autologous MSCs in subjects with obesity.

Original languageEnglish (US)
Pages (from-to)5926-5936
Number of pages11
JournalJournal of Cellular Physiology
Volume233
Issue number8
DOIs
StatePublished - Aug 2018

Keywords

  • mesenchymal stem cells
  • metabolic syndrome
  • mitochondria
  • obesity

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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