Dual effects of obesity on satellite cells and muscle regeneration

Physiol Rep. 2020 Aug;8(15):e14511. doi: 10.14814/phy2.14511.

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.

Keywords: muscle regeneration; obesity; satellite cell.

MeSH terms

  • Animals
  • Apoptosis
  • Cells, Cultured
  • Diet, High-Fat / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / physiology
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / pathology
  • Regeneration*
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Satellite Cells, Skeletal Muscle / physiology