Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.
OBJECTIVE
Interleukin-6 (IL-6) directly activates AMP-activated protein kinase (AMPK) in vivo and in vitro; however, the mechanism by which it does so is unknown.


METHODS
We examined this question in skeletal muscle using an incubated rat extensor digitorum longus (EDL) muscle preparation as a tool.


RESULTS
AMPK activation by IL-6 coincided temporally with a nearly threefold increase in the AMP:ATP ratio in the EDL. The effects of IL-6 on both AMPK activity and energy state were inhibited by coincubation with propranolol, suggesting involvement of beta-adrenergic signaling. In keeping with this notion, IL-6 concurrently induced a transient increase in cAMP, and its ability to activate AMPK was blocked by the adenyl cyclase inhibitor 2'5'-dideoxyadenosine. In addition, like other beta-adrenergic stimuli, IL-6 increased glycogen breakdown and lipolysis in the EDL. Similar effects of IL-6 on AMPK, energy state, and cAMP content were observed in C2C12 myotubes and gastrocnemius muscle in vivo, indicating that they were not unique to the incubated EDL.


CONCLUSIONS
These studies demonstrate that IL-6 activates AMPK in skeletal muscle by increasing the concentration of cAMP and, secondarily, the AMP:ATP ratio. They also suggest that substantial increases in IL-6 concentrations, such as those that can result from its synthesis by muscles during exercise, may play a role in the mobilization of fuel stores within skeletal muscle as an added means of restoring energy balance.
Kelly
Meghan
M
Department of Medicine, Section of Endocrinology, Diabetes Research Unit, Boston University School of Medicine, Boston, Massachusetts, USA.
Gauthier
Marie-Soleil
MS
Saha
Asish K
AK
Ruderman
Neil B
NB
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D050261:Glycogenolysis / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D015850:Interleukin-6; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; C534978:Prkaa2 protein, mouse; C543928:Prkaa2 protein, rat; D055372:AMP-Activated Protein Kinases