AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise.
Level 5 - mechanism / opinion, no new human data
Bench and animal model study without human participants
PubMed 15219849 · doi:10.1016/j.bbrc.2004.05.188
What was done
Researchers examined the effect of interleukin-6 (IL-6) on AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC) phosphorylation. In vitro, extensor digitorum longus muscle and cultured F422a adipocytes were incubated with IL-6 (30–120 ng/ml). In vivo, phosphorylation of AMPK (P-AMPK) and ACC (P-ACC) was measured in skeletal muscle, liver, and adipose tissue at rest and following exercise in 3-month-old IL-6 knockout (IL-6(-/-)) mice versus C57BL control mice.
What was found
Incubation with IL-6 (30–120 ng/ml) increased P-AMPK and P-ACC in isolated muscle and cultured adipocytes. In control mice, exercise increased P-AMPK and P-ACC abundance by 30% to 150% across muscle, liver, and adipose tissue. In IL-6(-/-) mice, baseline P-AMPK and P-ACC abundance was 60% to 90% lower in muscle and adipose tissue compared to controls, with more modest reductions in liver. Following exercise in IL-6(-/-) mice, absolute increases in P-AMPK were diminished in muscle and adipose tissue (though percentage increases were similar to controls), whereas liver responses were indistinguishable from controls.
Why it matters
This study provides mechanistic evidence that IL-6 released during muscle contraction directly promotes AMPK activation in muscle and adipose tissue, identifying a pathway through which myokines coordinate systemic metabolism during exercise.
Limits
The study was conducted entirely in rodent models and cultured cell lines, precluding direct clinical extrapolation. The abstract does not report animal sample sizes (n) or exact statistical confidence intervals. IL-6 deficiency did not completely abolish exercise-induced percentage increases in AMPK activation, indicating redundant non-IL-6 regulatory pathways.
Cited by
- partial Interleukin-6 released by exercising muscle is a key trigger for the activation of AMP kinase (AMPK).