title: High-fat feeding does not induce an autophagic or apoptotic phenotype in female rat skeletal muscle.
abstract: Apoptosis and autophagy are critical in normal skeletal muscle homeostasis; however, dysregulation can lead to muscle atrophy and dysfunction. Lipotoxicity and/or lipid accumulation may promote apoptosis, as well as directly or indirectly influence autophagic signaling. Therefore, the purpose of this study was to examine the effect of a 16-week high-fat diet on morphological, apoptotic, and autophagic indices in oxidative and glycolytic skeletal muscle of female rats. High-fat feeding resulted in increased fat pad mass, altered glucose tolerance, and lower muscle pAKT levels, as well as lipid accumulation and reactive oxygen species generation in soleus muscle; however, muscle weights, fiber type-specific cross-sectional area, and fiber type distribution were not affected. Moreover, DNA fragmentation and LC3 lipidation as well as several apoptotic (ARC, Bax, Bid, tBid, Hsp70, pBcl-2) and autophagic (ATG7, ATG4B, Beclin 1, BNIP3, p70 s6k, cathepsin activity) indices were not altered in soleus or plantaris following high-fat diet. Interestingly, soleus muscle displayed small increases in caspase-3, caspase-8, and caspase-9 activity, as well as higher ATG12-5 and p62 protein, while both soleus and plantaris muscle showed dramatically reduced Bcl-2 and X-linked inhibitor of apoptosis protein (XIAP) levels. In conclusion, this work demonstrates that 16 weeks of high-fat feeding does not affect tissue morphology or induce a global autophagic or apoptotic phenotype in skeletal muscle of female rats. However, high-fat feeding selectively influenced a number of apoptotic and autophagic indices which could have implications during periods of enhanced muscle stress.
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: Troy L
authors.initials: TL
authors.lastname: Campbell
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Mitchell
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: McMillan
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: Darin
authors.initials: D
authors.lastname: Bloemberg
authors.affiliation: School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Pavlov
authors.affiliation: School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Messa
authors.affiliation: School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Mielke
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L3G1, Canada jquadril@uwaterloo.ca
authors.forename: Joe
authors.initials: J
authors.lastname: Quadrilatero
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D059305:Diet, High-Fat; D005260:Female; D006019:Glycolysis; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: Apoptosis; autophagy; fiber type; gender; high-fat diet; skeletal muscle