High-fat feeding does not induce an autophagic or apoptotic phenotype in female rat skeletal muscle

• Published in: Experimental biology and medicine (Maywood, N.J.) N.J.), 2015-05, Vol.240 (5), p.657-668
• Main Authors: Campbell, Troy L, Mitchell, Andrew S, McMillan, Elliott M, Bloemberg, Darin, Pavlov, Dmytro, Messa, Isabelle, Mielke, John G, Quadrilatero, Joe
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Autophagy; Diet, High-Fat; Female; Glycolysis; Muscle, Skeletal - cytology; Muscle, Skeletal - immunology; Muscle, Skeletal - metabolism; Original Research; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/1535370214557223

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.