Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice
Open accessAbstract
Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation.
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Leptin is a pro-inflammatory adipokine; chronic exercise reduces circulating leptin levels and its associated inflammatory burden, contributing to an overall anti-inflammatory phenotype in physically trained individuals.
“Leptin is considered a pro-inflammatory adipokine; however, chronic exercise reduces circulating leptin levels and its associated inflammatory burden, thereby contributing to an overall anti-inflammatory phenotype in physically trained individuals”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [101]
The Introduction says leptin regulates immunity, but does not describe it as pro-inflammatory. The Discussion (Leptin Enhances Muscle Growth) says physical activity was not assessed; the passages found for inflammatory burden and chronic exercise do not address whether training lowers leptin or inflammation in humans. (LLM, conf=0.76)
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Long-Term PGC1β Overexpression Leads to Apoptosis, Autophagy and Muscle Wasting
Sopariwala, D. H., Yadav, V., Badin, P.-M., Likhite, N., Sheth, M., Lorca, S., Vila, I. K., Kim, E. R., Tong, Q., Song, M. S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10238-9 · Cited by 14 · see citing works
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Dunisławska, A., Siwek, M. Z., Sławińska, A., Lepczyński, A., Herosimczyk, A., Kolodziejski, P. A., & Bednarczyk, M. F. (2020) · Animals · doi:10.3390/ani10040687 · Cited by 12 · see citing works
- Authors
- Sáinz, N., Rodríguez, A., Catalán, V., Becerril, S., Ramírez, B., Gómez-Ambrosi, J., & Frühbeck, G.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Frühbeck, Gema
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-09-04
- Volume
- 4
- Issue
- 9
- Pages
- e6808
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2733298
- OpenAlex
- W2002233417
- Cited by
- 135
- References
- 92
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 10 · 2016: 6 · 2015: 7 · 2014: 13 · 2013: 15 · 2012: 11
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Gobierno de Navarra
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin, ob/ob mice, FOXO3, PGC-1α, atrogin-1, MuRF1, myostatin, muscle atrophy, muscle fiber type, myofibrillar protein degradation, muscle cell proliferation, cyclin D1, proliferating cell nuclear antigen, troponin T, skeletal muscle
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Forkhead Box Protein O3, Animals, Male, Mice, Inbred C57BL, Muscles, Transcription Factors, Trans-Activators, Proliferating Cell Nuclear Antigen, Cyclin D1, Troponin T, Oligonucleotide Array Sequence Analysis, Leptin, Gene Expression Profiling, Cell Proliferation, Mice, Forkhead Transcription Factors, Myostatin
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