Regulation of PERM1 and select target genes in human skeletal muscle following fasting and exercise

PERM1 has been identified as a key regulator of muscle energy metabolism, contractile function, and mitochondrial biogenesis. To investigate the impact fasting and acute and chronic high-intensity exercise on p38MAPK, pCaMKII, PGC-1α, ERRα, and PERM1 and on PERM1 target genes (CKMT2, GLUT4, and SIRT3) in human skeletal muscle. We performed secondary analyses of muscle biopsy samples from two previously published studies, and from one unpublished study. Muscle biopsies were analyzed from the following protocols: (1) nine men pre-, during, and post- an 8 h fast with or without 2 h of arm ergometer exercise; (2) nine men and eight women pre- and 3 h post-acute high-intensity interval cycling exercise (HIIE); and (3) eleven men and eight women pre- and post- a 6-week period of high-intensity interval training (HIIT) or nonexercise control. We used RT-PCR and Western blotting to determine the mRNA and protein levels, respectively. Immunolabelling, microscopy, and subcellular fractionation were also performed to assess PERM1 cellular localization. Fasting did not induce detectable changes in the PERM1-related pathways. HIIE significantly increased p-p38MAPK (p < 0.05, d = 1.27) protein, and PERM1 (p < 0.05, d = 0.781) and PGC-1α (p < 0.05, d = 1.51) mRNA. Six weeks of HIIT increased the protein levels of PERM1 isoform 2 (p < 0.05, ƞ² = 0.168) and CKMT2 (p < 0.05, ƞ² = 0.226). PERM1 was localized in the perinuclear region and enriched in the mitochondria. Our results suggest that only some components of PERM1-related pathways are preserved in human skeletal muscle, highlighting the importance of future studies examining PERM1 function in humans.