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Updated: Dec 12, 2025

Analyzing Satellite Cell Function During Skeletal Muscle Regeneration by Cardiotoxin Injury and Injection of Self-delivering siRNA In Vivo
Published on: September 18, 2019
Dual effects of obesity on satellite cells and muscle regeneration
Ashley E Geiger1, Morgan R Daughtry1, Con-Ning Yen1
1Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Abstract:
Obesity is a complex metabolic disorder that often leads to a decrease in insulin sensitivity, chronic inflammation, and overall decline in human health and well-being. In mouse skeletal muscle, obesity has been shown to impair muscle regeneration after injury; however, the mechanism underlying these changes has yet to be determined. To test whether there is a negative impact of obesity on satellite cell (SC) decisions and behaviors, we fed C57BL/6 mice normal chow (NC, control) or a high-fat diet (HFD) for 10 weeks and performed SC proliferation and differentiation assays in vitro. SCs from HFD mice formed colonies with smaller size (p < .001) compared to those from NC mice, and this decreased proliferation was confirmed (p < .05) by BrdU incorporation. Moreover, in vitro assays showed that HFD SCs exhibited diminished (p < .001) fusion capacity compared to NC SCs. In single fiber explants, a higher ratio of SCs experienced apoptotic events (p < .001) in HFD mice compared to that of NC-fed mice. In vivo lineage tracing using H2B-GFP mice showed that SCs from HFD treatment also cycled faster (p < .001) than their NC counterparts. In spite of all these autonomous cellular effects, obesity as triggered by high-fat feeding did not significantly impair muscle regeneration in vivo, as reflected by the comparable cross-sectional area (p > .05) of the regenerating fibers in HFD and NC muscles, suggesting that other factors may mitigate the negative impact of obesity on SCs properties.
Insights
High-fat diets impair mouse skeletal muscle stem cell (satellite cell) proliferation, fusion, and survival. However, obesity did not significantly hinder in vivo muscle regeneration, suggesting compensatory mechanisms.
Area of Science:
- Muscle biology
- Metabolic disorders
- Cellular regeneration
Background:
- Obesity is a complex metabolic disorder linked to insulin resistance and inflammation.
- Obesity negatively impacts skeletal muscle regeneration, but underlying mechanisms involving satellite cells are unclear.
Purpose of the Study:
- To investigate the impact of obesity on satellite cell (SC) behavior and function.
- To determine if obesity affects SC proliferation, differentiation, fusion, and apoptosis.
Main Methods:
- Mice were fed normal chow (NC) or a high-fat diet (HFD) for 10 weeks.
- In vitro assays assessed SC proliferation (BrdU incorporation) and differentiation (colony size, fusion capacity).
- In vivo lineage tracing (H2B-GFP mice) and single fiber explants evaluated SC apoptosis and cell cycle dynamics.
Main Results:
- HFD-induced obesity reduced SC colony size and proliferation compared to NC controls.
- HFD SCs showed diminished fusion capacity and increased apoptosis in vitro.
- In vivo, HFD SCs exhibited faster cycling, yet muscle regeneration cross-sectional area remained comparable between HFD and NC groups.
Conclusions:
- Obesity negatively impacts intrinsic satellite cell properties, including proliferation, fusion, and survival.
- Despite cellular deficits, obesity did not significantly impair overall in vivo muscle regeneration.
- Other factors likely compensate for obesity-induced satellite cell dysfunction in muscle repair.
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