The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration

J William Deaver; Eleanor R Schrems; Lemuel A Brown; Wesley A Haynie; Richard A Perry Jr; Megan E Rosa-Caldwell; Michelle A Tedrowe; Nicholas P Greene; Tyrone A Washington

doi:10.1016/j.smhs.2021.09.003

The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration

Sports Med Health Sci. 2021 Oct 12;3(4):212-217. doi: 10.1016/j.smhs.2021.09.003. eCollection 2021 Dec.

Authors

J William Deaver¹, Eleanor R Schrems², Lemuel A Brown², Wesley A Haynie², Richard A Perry Jr², Megan E Rosa-Caldwell¹, Michelle A Tedrowe², Nicholas P Greene¹, Tyrone A Washington²

Affiliations

¹ Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, 72701, USA.
² Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, 72701, USA.

Abstract

Diet-induced obesity has previously been shown to occur with the concomitant rise in the expression of proinflammatory cytokines and increases in collagen deposition. While it has been known that the regenerative process of skeletal muscle is altered in obese mice following an acute muscle injury, we sought to examine differences in the expression of various markers of extracellular matrix remodeling and repair. Our laboratory has previously reported an impaired inflammatory and protein synthetic signaling in these mice that may contribute negatively to the muscle regenerative process. To expand upon this previous investigation, tissues from these animals underwent further analysis to determine the extent of changes to the regenerative response within the extracellular matrix, including transcriptional changes in Collagen I, Collagen III, and Fibronectin. Here, we show that the expression of Collagen III:I is significantly increased at 3-days post-injury in obese injured animals compared to lean injured animals (p = 0.0338), and by 28-days the obese injured animals exhibit a significantly lower Collagen III:I than their lean injured counterparts (p = 0.0035). We demonstrate an impaired response to an acute muscle injury in obese mice when compared with lean counterparts. However, further studies are required to elucidate translational consequences of these changes, as well as to determine any causative mechanisms that may be driving this effect.

Keywords: Ct, Cycle Threshold; Diet induced obesity; ECM, Extracellular Matrix; Extracellular matrix remodeling; MMPs, Matrix Metalloproteinases; MRF, Myogenic Regulatory Factor; PBS, Phosphate Buffered Saline; Skeletal muscle; TA, Tibialis Anterior; TIMPs, Tissue Inhibitors of Metalloproteinases.