Studying intramuscular fat deposition and muscle regeneration: insights from a comparative analysis of mouse strains, injury models, and sex differences
Alessandra M. Norris, Kiara E. Fierman, Jillian Campbell, Rhea Pitale, Muhammad Shahraj, Daniel Kopinke
{"title":"Studying intramuscular fat deposition and muscle regeneration: insights from a comparative analysis of mouse strains, injury models, and sex differences","authors":"Alessandra M. Norris, Kiara E. Fierman, Jillian Campbell, Rhea Pitale, Muhammad Shahraj, Daniel Kopinke","doi":"10.1186/s13395-024-00344-4","DOIUrl":null,"url":null,"abstract":"Intramuscular fat (IMAT) infiltration, pathological adipose tissue that accumulates between muscle fibers, is a shared hallmark in a diverse set of diseases including muscular dystrophies and diabetes, spinal cord and rotator cuff injuries, as well as sarcopenia. While the mouse has been an invaluable preclinical model to study skeletal muscle diseases, they are also resistant to IMAT formation. To better understand this pathological feature, an adequate pre-clinical model that recapitulates human disease is necessary. To address this gap, we conducted a comprehensive in-depth comparison between three widely used mouse strains: C57BL/6J, 129S1/SvlmJ and CD1. We evaluated the impact of strain, sex and injury type on IMAT formation, myofiber regeneration and fibrosis. We confirm and extend previous findings that a Glycerol (GLY) injury causes significantly more IMAT and fibrosis compared to Cardiotoxin (CTX). Additionally, females form more IMAT than males after a GLY injury, independent of strain. Of all strains, C57BL/6J mice, both females and males, are the most resistant to IMAT formation. In regard to injury-induced fibrosis, we found that the 129S strain formed the least amount of scar tissue. Surprisingly, C57BL/6J of both sexes demonstrated complete myofiber regeneration, while both CD1 and 129S1/SvlmJ strains still displayed smaller myofibers 21 days post injury. In addition, our data indicate that myofiber regeneration is negatively correlated with IMAT and fibrosis. Combined, our results demonstrate that careful consideration and exploration are needed to determine which injury type, mouse model/strain and sex to utilize as preclinical model especially for modeling IMAT formation.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Skeletal Muscle","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13395-024-00344-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Intramuscular fat (IMAT) infiltration, pathological adipose tissue that accumulates between muscle fibers, is a shared hallmark in a diverse set of diseases including muscular dystrophies and diabetes, spinal cord and rotator cuff injuries, as well as sarcopenia. While the mouse has been an invaluable preclinical model to study skeletal muscle diseases, they are also resistant to IMAT formation. To better understand this pathological feature, an adequate pre-clinical model that recapitulates human disease is necessary. To address this gap, we conducted a comprehensive in-depth comparison between three widely used mouse strains: C57BL/6J, 129S1/SvlmJ and CD1. We evaluated the impact of strain, sex and injury type on IMAT formation, myofiber regeneration and fibrosis. We confirm and extend previous findings that a Glycerol (GLY) injury causes significantly more IMAT and fibrosis compared to Cardiotoxin (CTX). Additionally, females form more IMAT than males after a GLY injury, independent of strain. Of all strains, C57BL/6J mice, both females and males, are the most resistant to IMAT formation. In regard to injury-induced fibrosis, we found that the 129S strain formed the least amount of scar tissue. Surprisingly, C57BL/6J of both sexes demonstrated complete myofiber regeneration, while both CD1 and 129S1/SvlmJ strains still displayed smaller myofibers 21 days post injury. In addition, our data indicate that myofiber regeneration is negatively correlated with IMAT and fibrosis. Combined, our results demonstrate that careful consideration and exploration are needed to determine which injury type, mouse model/strain and sex to utilize as preclinical model especially for modeling IMAT formation.
期刊介绍:
The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators.
Main areas of interest include:
-differentiation of skeletal muscle-
atrophy and hypertrophy of skeletal muscle-
aging of skeletal muscle-
regeneration and degeneration of skeletal muscle-
biology of satellite and satellite-like cells-
dystrophic degeneration of skeletal muscle-
energy and glucose homeostasis in skeletal muscle-
non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies-
maintenance of neuromuscular junctions-
roles of ryanodine receptors and calcium signaling in skeletal muscle-
roles of nuclear receptors in skeletal muscle-
roles of GPCRs and GPCR signaling in skeletal muscle-
other relevant aspects of skeletal muscle biology.
In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission.
Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.