title: Dietary supplementation of β-guanidinopropionic acid (βGPA) reduces whole-body and skeletal muscle growth in young CD-1 mice.
abstract: Increased AMP-activated protein kinase (AMPK) activity leads to enhanced fatty acid utilization, while also promoting increased ubiquitin-dependent proteolysis (UDP) in mammalian skeletal muscle. β-guanidinopropionic acid (βGPA) is a commercially available dietary supplement that has been shown to promote an AMPK-dependent increase in fatty acid utilization and aerobic capacity in mammals by compromising creatine kinase function. However, it remains unknown if continuous βGPA supplementation can negatively impact skeletal muscle growth in a rapidly growing juvenile. The current study was conducted to examine the effect of βGPA supplementation on whole-body and skeletal muscle growth in juvenile and young adult mice. Three-week old, post weanling CD-1 mice were fed a standard rodent chow that was supplemented with either 2% (w/w) α-cellulose (control) or βGPA. Control and βGPA-fed mice (n = 6) were sampled after 2, 4, and 8 weeks. Whole-body and hindlimb muscle masses were significantly (P < 0.05) reduced in βGPA-fed mice by 2 weeks. The level of AMPK (T172) phosphorylation increased significantly (P < 0.05) in the gastrocnemius of βGPA-fed versus control mice at 2 weeks, but was not significantly different at the 4- and 8-week time points. Further analysis revealed a significant (P < 0.05) increase in the skeletal muscle-specific ubiquitin ligase MAFbx/Atrogin-1 protein and total protein ubiquitination in the gastrocnemius of βGPA versus control mice at the 8-week time point. Our data indicate that feeding juvenile mice a βGPA-supplemented diet significantly reduced whole-body and skeletal muscle growth that was due, at least in part, to an AMPK-independent increase in UDP.
authors.affiliation: Division of Natural Sciences and Engineering, University of South Carolina Upstate, 800 University Way, Spartanburg, SC, 29316, USA, bbaumgar@uscupstate.edu.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Baumgarner
authors.forename: Alison M
authors.initials: AM
authors.lastname: Nagle
authors.forename: Meagan R
authors.initials: MR
authors.lastname: Quinn
authors.forename: A Elaine
authors.initials: AE
authors.lastname: Farmer
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Kinsey
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D019587:Dietary Supplements; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D024510:Muscle Development / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development*; D011422:Propionates / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D006146:Guanidines; D046912:Multiprotein Complexes; D011422:Propionates; D025801:Ubiquitin; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C005775:guanidinopropionic acid