Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α

Bruce, Clinton R.; Dyck, David J.

doi:10.1152/ajpendo.00150.2004

Cited by 178Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismMuscle Physiology and Disorders

Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α

Bruce, Clinton R., Dyck, David J.·2004·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00150.2004

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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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Authors: Bruce, C. R., & Dyck, D. J.
Affiliations: University of Guelph (CA)
ORCID: Bruce, Clinton R.
Dyck, David J.
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
DOI: 10.1152/ajpendo.00150.2004
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › 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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Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α

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