AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise.
Abstract
Following exercise, AMP-activated protein kinase (AMPK) activity is increased several fold in rat liver and adipose tissue as well as muscle; however, the mechanism by which this occurs is not known. Interleukin-6 (IL-6) is released from muscle in large amounts during and after sustained physical activity resulting in up to 100-fold increases in its plasma concentration, from 1-2 ng/ml to 50-100 ng/ml. We report here that incubation with IL-6 (30-120 ng/ml) increases the phosphorylation of AMPK (an indicator of its activation) and that of its target molecule, acetyl CoA carboxylase (ACC), in both extensor digitorum longus muscle and cultured F422a adipocytes. To assess more directly whether IL-6 regulates AMPK in vivo during exercise, measurements were carried out in skeletal muscle, liver, and adipose tissue of 3-month-old IL-6 knockout (IL-6(-/-)) and C57 black control mice. In agreement with previous studies in the rat, in control mice P-AMPK and P-ACC abundance was increased by 30-150% in the three tissues in response to exercise with the greatest increases in skeletal muscle. In contrast, in IL-6(-/-) mice, we found that the abundance of both P-AMPK and P-ACC was lower (60-90%) in muscle and adipose tissue at rest. Also the absolute increases in P-AMPK caused by exercise were diminished compared to those in control mice, although percentage increases were similar. In liver, decreases in P-AMPK and P-ACC in the IL-6(-/-) mice were more modest and the increases in their abundance caused by exercise were indistinguishable from those of control mice. The results indicate that IL-6 can activate AMPK in muscle and adipose tissue, and that this contributes to, but does not fully account for, the increase in AMPK activity in these tissues in response to exercise. They also suggest that a genetic lack of IL-6 is associated with a decrease in AMPK activity.
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In rodents, IL-6 activates AMP-activated protein kinase (AMPK).
“In rodents, IL-6 has also been shown to activate AMP-activated protein kinase (AMPK) (37), a key enzyme involved in the activation of acetyl-coenzyme A carboxylase and lipid oxidation (38).”
From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [37]
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- Authors
- Kelly, M., Keller, C., Avilucea, P. R., Keller, P., Luo, Z., Xiang, X., Giralt, M., Hidalgo, J., Saha, A. K., Pedersen, B. K., & Ruderman, N. B.
- Affiliations
- Boston University (US)
- Rigshospitalet (DK)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Ruderman, Neil B.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 320
- Issue
- 2
- Pages
- 449-454
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2006332285
- Cited by
- 289
- References
- 37
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 13 · 2016: 12 · 2015: 17 · 2014: 16 · 2013: 20 · 2012: 22
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Boston University
- National Institutes of Health (5r01dk019514-35)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-19514)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- AMPK, interleukin-6, physical activity, IL-6 knockout mice, acetyl-CoA carboxylase, AMPK phosphorylation, skeletal muscle, adipose tissue, liver, energy metabolism
- MeSH terms
- Animals, Female, Liver, Multienzyme Complexes, Physical Conditioning, Animal, Interleukin-6, Protein Serine-Threonine Kinases, Adipocytes, Mice, Knockout, Muscle, Skeletal, Mice, Rats, AMP-Activated Protein Kinases
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