Collagen 3

Abstract

Obesity is a newly classified metabolic disease that can impair anabolic signaling during skeletal muscle regeneration. Optimal skeletal muscle regeneration includes inflammation and ECM remodeling. Disruption to any of these processes can negatively impact skeletal muscle regeneration. Previous literature has reported dysregulated signaling in the inflammatory response as well as a reduction in protein synthesis and myogenic regulatory factors in obese animal models. As a result, there is blunted skeletal muscle growth exhibited in these individuals. The extracellular matrix serves as a scaffold in skeletal muscle that is also used as a reservoir for proteins and growth factors that promote regeneration. PURPOSE: To determine how diet-induced obesity (DIO) alters ECM remodeling during skeletal muscle regeneration. METHODS: Forty-eight 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 administered PBS (uninjured) group or bupivacaine (injured) group. Three or 28 days post-injection, the TAs were extracted and PCR reaction was done to quantify ECM-related gene expression. RESULTS: Collagen-I gene expression was 12-fold and 17-fold greater in the lean and HFD 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 was 3-fold greater in the lean group and 43-fold greater in the HFD 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 55% reduction in collagen-III/I in the lean injured group, but a 4.5-fold increase in the HFD injured group (p < 0.05) 3 days post-bupivacaine injection. Collagen-III/I was 8-fold greater in the lean 28 days post-bupivacaine injection (p < 0.05), but there was no significant differences in obese uninjured and injured. CONCLUSIONS: Obesity reversed collagen III/I acutely during regeneration and was blunted 4 weeks following muscle damage. These findings suggest that obesity may negatively impact ECM composition thus reducing the capacity to regenerate skeletal muscle following injury.