Induction of Adiponectin in Skeletal Muscle by Inflammatory Cytokines: in Vivo and in Vitro Studies
Open accessAbstract
Adiponectin (ApN) is an adipocytokine that plays a fundamental role in energy homeostasis and counteracting inflammation. We examined whether ApN could be induced in a nonadipose tissue, the skeletal muscle, in vivo, and in cultured myotubes in response to lipopolysaccharides or proinflammatory cytokines. We next explored the underlying mechanisms. In vivo, injection of lipopolysaccharides to mice caused, after 24 h, an approximately 10-fold rise in ApN mRNA abundance and a concomitant 70% increase in ApN levels in tibialis anterior muscle. This ApN induction was reproduced in C2C12 myotubes cultured for 48 h with a proinflammatory cytokine combination, interferon-gamma + TNFalpha. This effect occurred in a time- and dose-dependent manner. Several pieces of evidence suggest that nitric oxide (NO) mediates this up-regulation by cytokines in myotubes or muscle. First, ApN was induced in vitro exclusively in the experimental conditions that stimulated NO production. Second, inducible NO synthase mRNA induction or NO production clearly preceded ApN mRNA induction. Third, preventing NO production by inhibitors of the NO synthases, nitro-L-arginine methyl ester or NG-methyl-L-arginine, suppressed the inductive effect of the cytokines in vitro and in vivo. Finally, ApN mRNA induction by cytokines was reproduced in cultured human myotubes. In conclusion, our data provide evidence that adiponectin is up-regulated in vivo and in vitro in human and rodent myotubes in response to inflammatory stimuli. The underlying mechanisms seem to involve a NO-dependent pathway. This overexpression may be viewed as a local antiinflammatory protection and a way to deliver extra energy supplies during inflammation.
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ApN can also be a true myokine.
“Besides being an adipokine, ApN can also be a true myokine [36,37].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [36]
ApN up-regulation was reproduced in cultured murine or human myotubes in response to pro-inflammatory cytokines, ROS inducers or triglycerides.
“ApN up-regulation was also reproduced in cultured murine or human myotubes in response to pro-inflammatory cytokines, reactive oxygen species (ROS) inducers or triglycerides [36,38].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [36]
Although mainly secreted by adipocytes under normal conditions, ApN may be produced in skeletal muscle of mice submitted to stressful challenges.
“Although it is mainly secreted by adipocytes under normal conditions, ApN may be produced in skeletal muscle of mice submitted to stressful challenges.”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [36]
Acute (LPS injection) or low-grade inflammation (genetic or nutritional induced obesity) enhanced ApN expression in muscle of challenged mice.
“Thus, acute (lipopolysaccharides (LPS) injection) or low-grade inflammation (genetic or nutritional induced obesity) enhanced ApN expression in muscle of challenged mice [36,38,39,40].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [36]
Myotubes from DMD patients were unable to produce ApN for local protection, unlike non-dystrophic myotubes challenged by inflammation.
“Moreover, myotubes from DMD patients were unable to produce ApN for local protection [57], unlike non-dystrophic myotubes challenged by inflammation [36].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [36]
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- Authors
- Delaigle, A. M., Jonas, J.-C., Bauche, I. B., Cornu, O., & Brichard, S. M.
- Affiliations
- UCLouvain (BE)
- Corresponding author
- Brichard, Sonia M.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-12
- Volume
- 145
- Issue
- 12
- Pages
- 5589-5597
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2050900577
- Cited by
- 241
- References
- 41
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 13 · 2023: 9 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 12 · 2018: 10 · 2017: 14 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 13 · 2012: 22
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adiponectin, skeletal muscle, inflammatory cytokines, lipopolysaccharide, nitric oxide, inducible nitric oxide synthase, interferon-gamma, TNF-α, myotubes, anti-inflammatory signaling, energy homeostasis, tibialis anterior
- MeSH terms
- Animals, Antineoplastic Agents, Cells, Cultured, Humans, Interferon-gamma, Lipopolysaccharides, Male, Mice, Inbred Strains, RNA, Messenger, Tumor Necrosis Factor-alpha, Gene Expression, Muscle, Skeletal, Myoblasts, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin, In Vitro Techniques
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