The effects of acute and chronic exercise on PGC ‐1α, irisin and browning of subcutaneous adipose tissue in humans
Open accessAbstract
Irisin was first identified as a peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) dependent myokine with the potential to induce murine brown-fat-like development of white adipose tissue. In humans, the regulatory effect of training on muscle FNDC5 mRNA expression and subsequently irisin levels in plasma is more controversial. We recruited 26 inactive men (13 normoglycaemic and normal weight, controls; and 13 slightly hyperglycaemic and overweight, pre-diabetes group) aged 40-65 years for a 12-week intervention of combined endurance and strength training with four sessions of training per week. Before and after the 12-week intervention period, participants were exposed to an acute endurance workload of 45 min at 70% of VO(2max), and muscle biopsies were taken prior to and after exercise. Skeletal muscle mRNA for PGC1A and FNDC5 correlated and both PGC1A and FNDC5 mRNA levels increased after 12 weeks of training in both control and pre-diabetes subjects. Circulating irisin was reduced in response to 12 weeks of training, and was increased acutely (~1.2-fold) just after acute exercise. Plasma concentration of irisin was higher in pre-diabetes subjects compared with controls. There was little effect of 12 weeks of training on selected browning genes in subcutaneous adipose tissue. UCP1 mRNA did not correlate with FNDC5 expression in subcutaneous adipose tissue or skeletal muscle or with irisin levels in plasma. We observed no enhancing effect of long-term training on circulating irisin levels, and little or no effect of training on browning of subcutaneous white adipose tissue in humans.
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In 26 physically inactive men (normoglycemic and diabetic) submitted to a 12-week physical training program combining strength and endurance exercises, muscle mRNA levels for both PGC-1α and FNDC5 were increased after exercise.
“Muscle biopsies were performed before and after the intervention and it was observed that muscle mRNA levels for both PGC-1α and FNDC5 were increased after exercise.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Norheim et al., 2014
The training-intervention and results sections report that 26 inactive men completed 12 weeks of combined strength and endurance training, after which skeletal-muscle PGC1A and FNDC5 mRNA increased. The second group had pre-diabetes, not diabetes. The results also distinguish the training effect from acute exercise, which did not increase FNDC5 expression in the first two hours. Page numbers are not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the same study, adipose tissue UCP1 mRNA levels were not directly correlated with FNDC5 levels in both adipose tissue and skeletal muscle.
“AT UCP1 mRNA levels were not directly correlated with FNDC5 levels in both AT and in SkM (Norheim et al., 2014).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Norheim et al., 2014
In the same study, circulating levels of irisin were only increased acutely and shortly after the exercise session (1.2-fold).
“However, circulating levels of irisin were only increased acutely and shortly after the exercise session (1.2-fold; Table 1).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Norheim et al., 2014
Norheim et al. demonstrated that UCP-1 mRNA did not correlate with gene expression of FNDC-5 in skeletal muscle, adipose tissue and serum irisin levels in response to endurance and resistance exercise training.
“Although Bostrom et al. [50] reported that irisin reduced body fat via increasing the expression of UCP-1 in adipose tissue, Norheim et al. [51] demonstrated that UCP-1 mRNA did not correlate with gene expression of FNDC-5 in skeletal muscle, adipose tissue and serum irisin levels in response to endurance and resistance exercise training.”
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Exercise-mediated effects on white and brown adipose tissue plasticity and metabolism
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- Authors
- Norheim, F., Langleite, T. M., Hjorth, M., Holen, T., Kielland, A., Stadheim, H. K., Gulseth, H. L., Birkeland, K. I., Jensen, J., & Drevon, C. A.
- Affiliations
- University of Oslo (NO)
- Norwegian School of Sport Sciences (NO)
- Oslo University Hospital (NO)
- Corresponding author
- Norheim, Frode
- ORCID
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2013-12-10
- Volume
- 281
- Issue
- 3
- Pages
- 739-749
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W2117031630
- Cited by
- 563
- References
- 41
- Citations by year
- 2026: 23 · 2025: 27 · 2024: 39 · 2023: 45 · 2022: 60 · 2021: 51 · 2020: 58 · 2019: 34 · 2018: 53 · 2017: 44 · 2016: 32 · 2015: 53 · 2014: 40 · 2013: 3
- FWCI
- 29.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (289511)
- Direktør Throne Holsts Fond For Ernæringsforskning
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- irisin, PGC-1α, FNDC5, white adipose tissue browning, subcutaneous adipose tissue, endurance training, resistance training, acute exercise, prediabetes, UCP1, myokines, skeletal muscle gene expression
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Adult, Aged, Fibronectins, Humans, Ion Channels, Male, Middle Aged, Motor Activity, Physical Endurance, Pigments, Biological, Prediabetic State, RNA, Messenger, Transcription Factors, Transcription, Genetic, Exercise, Body Mass Index, Muscle, Skeletal, Mitochondrial Proteins, Overweight, Subcutaneous Fat, Abdominal, Resistance Training
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