IL-6 and epinephrine have divergent fiber type effects on intramuscular lipolysis.
IL-6 is an exercise-regulated myokine that has been suggested to increase lipolysis in fast-twitch skeletal muscle. However, it is not known if a similar effect is present in slow-twitch muscle. Furthermore, epinephrine increases IL-6 secretion from skeletal muscle, suggesting that IL-6 could play a role in mediating the lipolytic effects of catecholamines. The purpose of this study was to determine whether IL-6 stimulates skeletal muscle lipolysis in a fiber type dependent manner and is required for epinephrine-stimulated lipolysis in murine skeletal muscle. Soleus and extensor digitorum longus (EDL) muscles from male C57BL/6J wild-type and IL-6(-/-) mice were incubated with 1 μM (183 ng/ml) epinephrine or 75 ng/ml recombinant IL-6 (rIL-6) for 60 min. IL-6 treatment increased 5'-AMP-activated protein kinase and signal transducer and activator of transcription 3 phosphorylation and glycerol release in isolated EDL but not soleus muscles from C57BL/6J mice. Conversely, epinephrine increased glycerol release in soleus but not EDL muscles from C57BL/6J mice. Basal lipolysis was elevated in soleus muscle from IL-6(-/-) mice, and this was associated with increases in adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58). The increase in ATGL content does not appear to be due to a loss of IL-6's direct effects, because ex vivo treatment with IL-6 failed to alter the expression of ATGL mRNA in soleus muscle. In summary, IL-6 stimulates lipolysis in glycolytic but not oxidative muscle, whereas the opposite fiber type effect is seen with epinephrine. The absence of IL-6 indirectly upregulates lipolysis, and this is associated with increases in ATGL and its coactivator CGI-58.
Department of Human Health and Nutritional Science, University of Guelph, Guelph, Ontario, Canada.
Tara L
TL
Macdonald
Zhongxiao
Z
Wan
Scott
S
Frendo-Cumbo
David J
DJ
Dyck
David C
DC
Wright
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D006019:Glycolysis; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010641:Phenotype; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D000217:Acyltransferases
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D055372:AMP-Activated Protein Kinases; D004837:Epinephrine; D005990:Glycerol; D015850:Interleukin-6; D008049:Lipase; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
IL-6 knockout; adipose triglyceride lipase; epinephrine; extensor digitorum longus; hormone-sensitive lipase; murine; soleus