IL-15 improves skeletal muscle oxidative metabolism and glucose uptake in association with increased respiratory chain supercomplex formation and AMPK pathway activation.
Biochim Biophys Acta Gen Subj
; 1863(2): 395-407, 2019 02.
Article
in En
| MEDLINE
| ID: mdl-30448294
ABSTRACT
BACKGROUND:
IL-15 is believed to play a role in the beneficial impact of exercise on muscle energy metabolism. However, previous studies have generally used supraphysiological levels of IL-15 that do not represent contraction-induced IL-15 secretion.METHODS:
L6 myotubes were treated acutely (3â¯h) and chronically (48â¯h) with concentrations of IL-15 mimicking circulating (1-10â¯pg/ml) and muscle interstitial (100â¯pg/ml -20â¯ng/ml) IL-15 levels with the aim to better understand its autocrine/paracrine role on muscle glucose uptake and mitochondrial function.RESULTS:
Acute exposure to IL-15 levels representing muscle interstitial IL-15 increased basal glucose uptake without affecting insulin sensitivity. This was accompanied by increased mitochondrial oxidative functions in association with increased AMPK pathway and formation of complex III-containing supercomplexes. Conversely, chronic IL-15 exposure resulted in a biphasic effect on mitochondrial oxidative functions and ETC supercomplex formation was increased with low IL-15 levels but decreased with higher IL-15 concentrations. The AMPK pathway was activated only by high levels of chronic IL-15 treatment. Similar results were obtained in skeletal muscle from muscle-specific IL-15 overexpressing mice that show very high circulating IL-15 levels.CONCLUSIONS:
Acute IL-15 treatment that mimics local IL-15 concentrations enhances muscle glucose uptake and mitochondrial oxidative functions. That mitochondria respond differently to different levels of IL-15 during chronic treatments indicates that IL-15 might activate two different pathways in muscle depending on IL-15 concentrations. GENERALSIGNIFICANCE:
Our results suggest that IL-15 may act in an autocrine/paracrine fashion and be, at least in part, involved in the positive effect of exercise on muscle energy metabolism.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muscle, Skeletal
/
Cell Respiration
/
Interleukin-15
/
AMP-Activated Protein Kinases
/
Glucose
/
Mitochondria
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Biochim Biophys Acta Gen Subj
Year:
2019
Type:
Article
Affiliation country:
Canada