Michelle A. Tedrowe, Lemuel A. Brown, Richard A. Perry Jr., Megan E. Rosa, Jacob L. Brown, David E. Lee, Nicholas P. Greene, Tyrone A. Washington. University of Arkansas, Fayetteville, Arkansas; email: matedrow@uark.edu

Obesity negatively effects skeletal muscle’s regenerative capacity. Optimal skeletal muscle regeneration includes inflammation, ECM remodeling, and myofiber growth. Disruption to any of these processes can negatively affect skeletal muscle regeneration. The extracellular matrix (ECM) acts as a scaffold for skeletal muscle fibers and also serves as a reservoir for proteins and growth factors that promote regeneration. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade collagen fibrils within the ECM. MMP-2 and 9 are the most abundant in skeletal muscle. PURPOSE: To determine if obesity alters MMP gene expression at the onset of skeletal muscle regeneration. METHODS: Twenty male C57BL6/J mice were randomly assigned to two groups: lean diet (10% fat) and high fat diet (HFD) (60% fat). Within those two groups, mice were randomly assigned to either a PBS (uninjured) group or a bupivacaine (injured) group. Bupivacaine is a myotoxin which induces injury to skeletal muscle. Bupivacaine or PBS was injected into the tibialis anterior (TA). Three days post-injection, the TAs were extracted and quantitative PCR was done to determine MMP-2 and MMP-9 gene expression. RESULTS: There was a significant decrease in TA muscle mass to body weight ratio in lean group (1.8 ± 0.06 mg/g vs. 1.6 ± 0.05 mg/g, p < 0.05) and the HFD group (1.5 ± 0.1 mg/g, vs. 1.4 ± 0.1 mg/g p < 0.05) 3 days post-injection. There was a 70% reduction in the collagen-III:I ratio in the lean injured group compared to the lean uninjured group (p < 0.05) 3 days post-injection. However, there was a 4.5-fold increase in the collagen III:I ratio in the HFD injured group compared to the HFD uninjured group (p < 0.05) 3 day post-injection. Obesity alone did not affect MMP-2 or 9 gene expression. There was no difference in MMP-2 gene expression (p > 0.05) 3 days post-injection. There was a main effect of injury to increase MMP-9 (p < 0.05) gene expression 3 day post-injection regardless of diet. CONCLUSION: Collagen III:I ratio differed between lean and obese at the onset of regeneration. It does not appear that MMPs 2 and 9 are responsible for this change in collagen III:I ratio. Future studies can include looking at other MMPs that play a role in skeletal muscle and other factors that may affect the change in collagen III:I ratio.

Funding provided by a grant from the American Biosciences Institute

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