title: Diet-induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration.
abstract: OBJECTIVE
  Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors (MRFs) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice.
  
  
  METHODS
  Forty-eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high-fat diet (HFD, 60% fat) or a lean diet (10% fat) for 12 weeks. At 15 weeks, bupivacaine was injected into the tibialis anterior (TA) of the injured group (n = 5-8/group) and PBS was injected into the control (n = 5-6). The TA was excised 3 or 28 days after injection.
  
  
  RESULTS
  We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced IL-6, MyoD and IGF-1 mRNA abundance compared to the lean mice (P < 0.05). Three days following muscle damage, TNF-α mRNA and protein levels of P-STAT3 and P-Akt were 14-fold, fourfold and fivefold greater in the lean mice respectively. However, there were no differences observed in the obese injured group compared to the uninjured group. Moreover, p70S6K1 was threefold greater in lean injured mice compared to uninjured but was reduced by 28% in the obese injured mice.
  
  
  CONCLUSIONS
  Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.
authors.affiliation: Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Brown
authors.affiliation: Integrative Muscle Metabolism Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Patton
authors.affiliation: Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Perry
authors.affiliation: Integrative Muscle Metabolism Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Brown
authors.affiliation: Department of Food Science, University of Arkansas, Fayetteville, AR, USA.
authors.forename: J I
authors.initials: JI
authors.lastname: Baum
authors.affiliation: Eleanor Mann School of Nursing, University of Arkansas, Fayetteville, AR, USA.
authors.forename: N
authors.initials: N
authors.lastname: Smith-Blair
authors.affiliation: Integrative Muscle Metabolism Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Greene
authors.affiliation: Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Washington
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I
keywords: diet-induced obesity; inflammation; protein synthesis; regeneration; skeletal muscle