The truncated splice variants, NT -PGC -1α and PGC -1α4 , increase with both endurance and resistance exercise in human skeletal muscle
Open accessAbstract
Recently, a truncated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) splice variant, PGC-1α4, that originates from the alternative promoter was shown to be induced by resistance exercise and to elicit muscle hypertrophy without coactivation of "classical" PGC-1α targets involved in mitochondrial biogenesis and angiogenesis. In order to test if distinct physiological adaptations are characterized by divergent induction of PGC-1α splice variants, we investigated the expression of truncated and nontruncated PGC-1α splice variants and PGC-1α transcripts originating from the alternative and the proximal promoter, in human skeletal muscle in response to endurance and resistance exercise. Both total PGC-1α and truncated PGC-1α mRNA expression were increased 2 h after endurance (P < 0.01) and resistance exercise (P < 0.01), with greater increases after endurance exercise (P < 0.05). Expression of nontruncated PGC-1α increased significantly in both exercise groups (P < 0.01 for both groups) without any significant differences between the groups. Both endurance and resistance exercise induced truncated as well as nontruncated PGC-1α transcripts from both the alternative and the proximal promoter. Further challenging the hypothesis that induction of distinct PGC-1α splice variants controls exercise adaptation, both nontruncated and truncated PGC-1α transcripts were induced in AICAR-treated human myotubes (P < 0.05). Thus, contrary to our hypothesis, resistance exercise did not specifically induce the truncated forms of PGC-1α. Induction of truncated PGC-1α splice variants does not appear to underlie distinct adaptations to resistance versus endurance exercise. Further studies on the existence of numerous splice variants originating from different promoters are needed.
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Others have failed to show a specificity of adaptation response in PGC-1α isoforms with acute bouts of endurance compared to resistance exercise or differences in expression with resistance versus concurrent exercise bouts in untrained individuals.
“However, in contrast to the early results from Ruas et al. (Ruas et al., 2012), others have failed to show a specificity of adaptation response in PGC-1α isoforms with acute bouts of endurance compared to resistance exercise or indeed differences in expression with resistance versus concurrent exercise bouts albeit in untrained individuals (Ydfors et al., 2013;Lundberg et al., 2014a).”
From Concurrent exercise training: do opposites distract? (2017) · cites this paper as Ydfors et al., 2013
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Experimental — accuracy not yet measuredSex appears to affect exercise-induced expression of pgc1α4.
“For example, sex appears to affect exercise-induced expression of pgc1α4. Indeed, recent data demonstrate that acute bouts of both ET and RT increase the expression of pgc1α4 in men (26).”
From Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age (2015) · cites this paper as [26]
Increased OXPHOS in response to ET and CT is mediated in part by PGC1α.
“Both mRNA and protein abundance of PGC1α generally increased in response to ET and CT, showing similar directions of change in both age groups but reaching statistical significance specifically in the young; this finding supports the notion that increased OXPHOS in response to ET and CT is mediated in part by PGC1α, which is a master regulator of mitochondrial biogenesis (26).”
From Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age (2015) · cites this paper as [26]
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- Authors
- Ydfors, M., Fischer, H., Mascher, H., Blomstrand, E., Norrbom, J., & Gustafsson, T.
- Affiliations
- Karolinska Institutet (SE)
- Department of Laboratory Medicine; Karolinska Institutet; Stockholm Sweden
- Swedish School of Sport and Health Sciences (SE)
- Corresponding author
- Norrbom, Jessica
- Venue
- Physiological Reports
- Publisher
- Wiley
- Published
- 2013-11
- Volume
- 1
- Issue
- 6
- Pages
- e00140
- ISSN
- 2051-817X (ISSN-L)
- PMC
- PMC3871455
- OpenAlex
- W2123118174
- Cited by
- 77
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 8 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 13
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Physiological Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Diva portal (Dalarna University Library) (submittedVersion, other-oa)
- Funders
- Swedish National Centre for Research in Sports
- Swedish Medical Association
- Karolinska Institutet Foundation
- Wallenberg Foundation
- Trygg-Hansa Foundation
- Åke Wiberg Foundation
- Magnus Bergvall Foundation
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- PGC-1α, alternative promoters, endurance exercise, resistance training, skeletal muscle, exercise adaptation, AICAR, myotubes, muscle hypertrophy, mitochondrial biogenesis
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