The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α
Abstract
IL-6 and TNF-alpha have been associated with insulin resistance and type 2 diabetes. Furthermore, abnormalities in muscle fatty acid (FA) metabolism are strongly associated with the development of insulin resistance. However, few studies have directly examined the effects of either IL-6 or TNF-alpha on skeletal muscle FA metabolism. Here, we used a pulse-chase technique to determine the effect of IL-6 (50-5,000 pg/ml) and TNF-alpha (50-5,000 pg/ml) on FA metabolism in isolated rat soleus muscle. IL-6 (5,000 pg/ml) increased exogenous and endogenous FA oxidation by approximately 50% (P < 0.05) but had no effect on FA uptake or incorporation of FA into endogenous lipid pools. In contrast, TNF-alpha had no effect on FA oxidation but increased FA incorporation into diacylglycerol (DAG) by 45% (P < 0.05). When both IL-6 (5,000 pg/ml) and insulin (10 mU/ml) were present, IL-6 attenuated insulin's suppressive effect on FA oxidation, increasing exogenous FA oxidation (+37%, P < 0.05). Furthermore, in the presence of insulin, IL-6 reduced the esterification of FA to triacylglycerol by 22% (P < 0.05). When added in combination with IL-6 or leptin (10 microg/ml), the TNF-alpha-induced increase in DAG synthesis was inhibited. In conclusion, the results demonstrate that IL-6 plays an important role in regulating fat metabolism in muscle, increasing rates of FA oxidation, and attenuating insulin's lipogenic effects. In contrast, TNF-alpha had no effect on FA oxidation but increased FA incorporation into DAG, which may be involved in the development of TNF-alpha-induced insulin resistance in skeletal muscle.
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“and causes hepatic and muscle insulin resistance in humans and in mice (39,55-60).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [56]
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“Several other studies have described that IL-6 can increase intramyocellular (58-60) or whole body (61) fatty acid oxidation via AMPK activation (58, 62).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [59]
In the citing paper
“Of note, whereas it is known that both TNF-α and IL-6 induce lipolysis [40, 49], only IL-6 appears to induce fat oxidation [19, 59].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [59]
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Metadata
- Authors
- Bruce, C. R., & Dyck, D. J.
- Affiliations
- University of Guelph (CA)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2004-10
- Volume
- 287
- Issue
- 4
- Pages
- E616-E621
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2128600629
- Cited by
- 178
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 11 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 7 · 2013: 13 · 2012: 15
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- interleukin-6, TNF-α, skeletal muscle, fatty acid metabolism, fatty acid oxidation, insulin resistance, type 2 diabetes, diacylglycerol synthesis, triacylglycerol esterification, leptin, soleus muscle, lipogenesis
- MeSH terms
- Animals, Diglycerides, Fatty Acids, Female, Insulin Resistance, Kinetics, Oxidation-Reduction, Palmitates, Triglycerides, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Rats, Sprague-Dawley, Muscle, Skeletal, Leptin, Rats, In Vitro Techniques
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