sciencemag.org SCIENCEPHOTO: KLEIN AND HUBERT/MINDEN PICTURESBy Jorge C. Correia and Jorge L. RuasE
xercise is important for human health.
Many of the beneficial effects of ex-
ercise come from the activation of
metabolism to drive muscle contrac-
tion, which mobilizes and utilizes fuel
stores and promotes healthy systemic
energy homeostasis. Conversely, sedentary
behaviors are linked to higher incidence of
diseases such as diabetes and cardiovascu-
lar disorders, but also neurodegeneration
and certain types of cancer^ ( 1 ). For these
reasons, identifying the molecular media-
tors of the benefits of exercise could provide
new therapeutic tools to fight many chronic
diseases. On page 488 of this issue, Knudsen
et al. ( 2 ) report that the cytokine interleu-
kin-13 (IL-13) is produced in mouse skeletal
muscle tissue and increases with exercise.
This cytokine is necessary for the metabolic
adaptation to exercise and enhances endur-
ance and systemic metabolism in mice.The complexity of skeletal muscle is
often overlooked. In addition to muscle
fibers, skeletal muscle has many other
resident cells such as muscle stem cells
(satellite cells), myoblasts, fibroblasts, fi-
bro-adipogenic precursors (a specialized
mesenchymal cell), endothelial cells, and
immune cells. Adaptation to exercise train-
ing depends on proficient communication
between them, often through secreted fac-
tors or “exerkines”. To date, most efforts to
identify exerkines have focused on factors
secreted by muscle fibers, called myokines.
These can have autocrine, paracrine, and/
or endocrine actions and affect muscle size
and strength, systemic energy expenditure,
immunity, and mental health, among oth-
ers (3, 4). The findings of Knudsen et al.
establish that IL-13, potentially secreted by
type 2 innate lymphoid cells (ILC2s) within
the skeletal muscle, elicits metabolic repro-
graming in skeletal muscle fibers. ILC2s
are a type of immune cell mainly associ-
ated with immune responses to allergens
and helminth infections. Identified only a
decade ago, ILC2s are emerging as key regu-
lators of metabolic homeostasis, tissue re-generation, and fibrosis ( 5 ). These findings
further implicate these cells at the interface
between immunity and muscle metabolism.
Muscle contraction requires high
amounts of energy, mainly provided by
oxidation of glucose and fatty acids. These
fuels can be stored in muscle fibers or mo-
bilized from liver and adipose tissue. The
choice of which fuel to oxidize during en-
durance exercise depends on factors such
as exercise duration and intensity, and the
training state of the individual ( 6 ). This is
the case for both rodents and humans. For
example, in individuals who exercise at
mild to moderate intensities, muscle fibers
use fatty acid oxidation almost exclusively.
Prioritizing fatty acid utilization until the
supply and transport to skeletal muscle be-
comes limiting conserves glucose stores (as
glycogen) for later stages of performance.
Exercise training not only delays the
switch to glucose oxidation but also makes
it more energy efficient ( 6 , 7 ).
Knudsen et al. show that IL-13 in skel-
etal muscle is important for this metabolic
flexibility. Indeed, mice in which the Il13
gene was deleted preferentially used mus-Molecular and Cellular Exercise Physiology, Department
of Physiology and Pharmacology, Biomedicum, Karolinska
Institutet, 171 77 Stockholm, Sweden. Email: [email protected]INSIGHTS | PERSPECTIVESMETABOLISMExercised cytokines
promote endurance
Muscle tissue secretory response to
exercise promotes beneficial metabolism
470 1 MAY 2020 • VOL 368 ISSUE 6490jxs