Journal article
Lack of Skeletal Muscle IL-6 Affects Pyruvate Dehydrogenase Activity at Rest and during Prolonged Exercise
Section for cell biology and physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.1
Pyruvate dehydrogenase (PDH) plays a key role in the regulation of skeletal muscle substrate utilization. IL-6 is produced in skeletal muscle during exercise in a duration dependent manner and has been reported to increase whole body fatty acid oxidation, muscle glucose uptake and decrease PDHa activity in skeletal muscle of fed mice.
The aim of the present study was to examine whether muscle IL-6 contributes to exercise-induced PDH regulation in skeletal muscle. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice and floxed littermate controls (control) completed a single bout of treadmill exercise for 10, 60 or 120 min, with rested mice of each genotype serving as basal controls.
The respiratory exchange ratio (RER) was overall higher (P<0.05) in IL-6 MKO than control mice during the 120 min of treadmill exercise, while RER decreased during exercise independent of genotype. AMPK and ACC phosphorylation also increased with exercise independent of genotype. PDHa activity was in control mice higher (P<0.05) at 10 and 60 min of exercise than at rest but remained unchanged in IL-6 MKO mice.
In addition, PDHa activity was higher (P<0.05) in IL-6 MKO than control mice at rest and 60 min of exercise. Neither PDH phosphorylation nor acetylation could explain the genotype differences in PDHa activity. Together, this provides evidence that skeletal muscle IL-6 contributes to the regulation of PDH at rest and during prolonged exercise and suggests that muscle IL-6 normally dampens carbohydrate utilization during prolonged exercise via effects on PDH.
| Language: | English |
|---|---|
| Publisher: | Public Library of Science |
| Year: | 2016 |
| Pages: | e0156460 |
| ISSN: | 19326203 , 15537358 and 1553734x |
| Types: | Journal article |
| DOI: | 10.1371/journal.pone.0156460 |
| ORCIDs: | Bertholdt, Lærke and Pilegaard, Henriette |
Acetyl-CoA Carboxylase Adenylate Kinase Animals Blood Glucose Blotting, Western Calorimetry Cell Respiration Fatty Acids Glucose-6-Phosphate Glycogen Hexokinase Interleukin-6 Lactates Male Medicine Mice, Inbred C57BL Mice, Knockout Muscle, Skeletal Oxidative Phosphorylation Phosphorylation Physical Conditioning, Animal Physical Endurance Pyruvate Dehydrogenase (Lipoamide) Q R RNA, Messenger Rest STAT3 Transcription Factor Science Sirtuin 3 Socs3 protein, mouse Suppressor of Cytokine Signaling 3 Protein
