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Transcriptional activation of the IL‐6 gene in human contracting skeletal muscle: influence of muscle glycogen content
Author(s) -
Keller Charlotte,
Steensberg Adam,
Pilegaard Henriette,
Osada Takuya,
Saltin Bengt,
Pedersen Bente Klarlund,
Neufer P. Darrell
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0507fje
Subject(s) - glycogen , skeletal muscle , medicine , endocrinology , glycogen synthase , gene expression , myocyte , biology , chemistry , gene , biochemistry
In humans, the plasma interleukin 6 (IL‐6) concentration increases dramatically during low‐intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL‐6 production. To determine whether energy availability influences the regulation of IL‐6 expression during prolonged exercise, six male subjects completed two trials consisting of 180 min of two‐legged dynamic knee extensor with either normal or low (~60% of control) pre‐exercise muscle glycogen levels. Increases in plasma IL‐6 during exercise were significantly higher ( P < 0.05) in the low‐glycogen (16‐fold) trial verses the control (10‐fold) trial. Transcriptional activation of the IL‐6 gene in skeletal muscle was also higher in the low‐glycogen trial; it increased by about 40‐fold after 90 min of exercise and about 60‐fold after 180 min of exercise. Muscle IL‐6 mRNA followed a similar but delayed pattern, increasing by more than 100‐fold in the low‐glycogen trial and by about 30‐fold in the control trial. These data demonstrate that exercise activates transcription of the IL‐6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. These findings also support the hypothesis that IL‐6 may be produced by contracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.