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

Skeletal muscle has the ability to regenerate from damage; however, recent studies have reported a negative effect of obesity on skeletal muscle regenerative capacity. The extracellular matrix (ECM) contributes to skeletal muscle structure acting as a scaffold for skeletal muscle. Additionally, skeletal muscle serves as a reservoir for proteins and growth factors that promote regeneration. Optimal skeletal muscle regeneration includes inflammation, ECM remodeling, and myofiber growth. Disruptions to any of these processes can negatively affect skeletal muscle regeneration. PURPOSE: To determine how diet-induced obesity (DIO) affects ECM remodeling during skeletal muscle regeneration. METHODS: Fifty-six male C57BL/6J 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. Both groups received injections into the tibialis anterior (TA). Three or 28 days post-bupivacaine injection, the TAs were extracted and PCR reaction was done to quantify ECM-related gene expression. RESULTS: The mice on the HFD had a 52% increase in bodyweight compared to the lean control (lean = 25.7 g ± 0.3, HFD = 39.2 g ± 1.4, p < 0.05). There was a significant decrease in TA muscle mass to bodyweight ratio in the lean group (1.8 ± 0.06 mg/g vs. 1.7 ± 0.03 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-bupivacaine injection. There was a significant increase in TA muscle mass to bodyweight ratio in lean group (1.9 ± 0.1 mg/g vs. 2.2 ± 0.1 mg/g, p < 0.05) and this was not observed in the HFD group (1.3 ± 0.1 mg/g, vs. 1.3 ± 0.1 mg/g) 28 days post-bupivacaine injection. There was a 12-fold and 4-fold increase in collagen-I gene expression in the lean and high-fat groups, respectively 3 days post-bupivacaine injection (p < 0.05). There was a main effect of injury to decrease collagen-I gene expression 28 days post-bupivacaine-injection (p < 0.05). Collagen-III gene expression increased 3-fold in the lean group and a 19-fold increase in the high-fat group (p < 0.05) 3 day post-bupivacaine injection. There were no differences in collagen-III gene expression 28 days post-bupivacaine injection. There was a 70% reduction in the collagen-III/I ratio in the lean injured group, but a 4.5-fold increase in the HFD injured group (p < 0.05) 3 day post-bupivacaine injection. CONCLUSION: Obesity altered the ECM composition during skeletal muscle regeneration. This could negatively impact the ability of obese muscle to recovery form injury.

This work was supported by a grant from the American Biosciences Institute.

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