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

Area of Science:

• Stem cell biology
• Mitochondrial medicine
• Obesity research

Background:

• Autologous mesenchymal stem cells (MSCs) show therapeutic potential but their efficacy relies on mitochondrial function.
• Mitochondria can be compromised in adverse conditions, potentially impacting MSC function.
• Obesity is a growing health concern with potential systemic effects on cellular function.

Purpose of the Study:

• To investigate the impact of obesity on the mitochondrial structure and function of MSCs.
• To explore the potential role of micro-RNAs (miRNAs) in mediating obesity-induced mitochondrial dysfunction in MSCs.
• To assess the implications of these alterations for the therapeutic application of MSCs.

Main Methods:

• MSCs were isolated from lean and obese swine.
• Mitochondrial structure was analyzed using electron microscopy.
• Mitochondrial function was assessed via membrane potential and Cytochrome-c oxidase (COX)-IV activity assays.
• Oxidative stress was measured using Mito-SOX and dihydroethidium staining.
• miRNA expression profiling was conducted using RNA-sequencing (RNA-seq).

Main Results:

• Obese-MSCs exhibited smaller mitochondria with altered cristae structure compared to Lean-MSCs.
• Mitochondrial membrane potential and COX-IV activity were reduced in Obese-MSCs.
• Increased mitochondrial oxidative stress was observed in Obese-MSCs.
• RNA-seq identified 5 upregulated miRNAs in Obese-MSCs targeting 43 mitochondrial genes.

Conclusions:

• Obesity negatively impacts MSC mitochondrial structure and function.
• miRNA dysregulation may contribute to obesity-induced mitochondrial impairment in MSCs.
• These mitochondrial alterations in Obese-MSCs could limit their therapeutic efficacy.