Inflammatory Signaling is Altered in Sarcopenic Obese Mice During Skeletal Muscle Regeneration
Authors: Brown Lemuel A , Perry Richard A , Haynie Wesley , Brown Jacob L. , Rosa‐Caldwell Megan E. , Lee David E. , Greene Nicholas P. , Washington Tyrone A 
Published: November 2023

Currently, sarcopenic obesity is a major concern because older adults are the fastest growing obese population in the United States. Sarcopenic obese individuals exhibit excess adipose tissue along with a decline in skeletal muscle mass and associated muscle weakness that contribute to reduced mobility and muscle recovery. The inflammatory process is a major regulator in skeletal muscle regeneration. This process is critical for optimal recovery following muscle damage. The regenerative process is also dependent on the activation of myogenic regulatory factors (MRFs) for optimal muscle growth which is partially regulated by inflammatory signaling. It has been demonstrated in both aging and obese individuals that there is sub‐optimal regeneration partially due to altered inflammatory signaling. Yet, little is known about skeletal muscle regeneration in the comorbidity of sarcopenic obesity.

Purpose

to determine how sarcopenic obesity alters MRFs and inflammatory signaling during muscle regeneration in mice.

Methods

One hundred two male C57BL6/J mice (4 weeks old) were randomly assigned to either a high fat diet (HFD, 60% fat) or normal chow and were fed ad libitum. Both young (12 weeks) and aged mice (22–24 months old) were injected with either PBS (control) or bupivacaine (myotoxin) in the tibialis anterior (TA). The TA was excised 3 or 21 days after injection. Fiber size distribution was examined by chi‐square analysis. Protein and gene expression data were analyzed by two‐way ANOVA and post hoc LSD test.

Results

Bodyweight in the young HFD mice was 21% greater than the young lean mice (p < 0.05). Bodyweight in the aged HFD mice was 38% greater than the aged lean mice (p < 0.05). Mean cross‐sectional area was 20% greater in the young lean injured mice compared to young lean uninjured mice 21 days post‐injection (p < 0.05). Mean cross‐sectional area was 9% greater in the aged lean injured mice compared to aged lean uninjured mice 21 days post‐injection (p < 0.05). However, there were no changes in the young and aged HFD injured mice compared to their uninjured controls 21 days post‐injection. There were no reported changes in MRF gene expression in aged HFD mice 3 and 21 days post‐injection. IL‐6 gene expression was 3‐fold greater than the uninjured group in aged HFD mice 3 days post‐bupivacaine injection (p < 0.05). Three days post‐injection, there was a main effect of diet with a decrease of TNF‐α gene expression in the aged HFD mice (p < 0.05). Three days post‐injection, there was a main effect of diet to increase NF‐κB in the aged HFD mice (p < 0.05). NF‐κB was 3‐fold greater in the aged HFD injured mice compared to the uninjured mice 21 days post‐bupivacaine injection (p < 0.05).

Conclusion

Sarcopenic obese mice had reduced regenerative capacity due to impaired inflammatory signaling.

Support or Funding Information

This work was supported by Rigel Pharmaceuticals and the Arkansas Biosciences Institute.