TY - JOUR

T1 - Interleukin 6 as an energy allocator in muscle tissue

AU - Kistner, Timothy M.

AU - Pedersen, Bente K.

AU - Lieberman, Daniel E.

PY - 2022

Y1 - 2022

N2 - Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict that during bouts of physical activity, myokine IL-6 fulfills the three main characteristics of a short-term energy allocator: it is secreted from muscle in response to an energy deficit, it liberates somatic energy through lipolysis and it enhances muscular energy uptake and transiently downregulates immune function. We then extend this model of energy allocation beyond myokine IL-6 to reinterpret the roles that IL-6 plays in chronic inflammation, as well as during COVID-19-associated hyperinflammation and multiorgan failure.Interleukin 6 is a pleiotropic cytokine that can be pro- or anti-inflammatory, depending on the metabolic context. Kistner et al. propose that these context-dependent effects are due to its adaptive role for short-term energy allocation, particularly during physical activity.

AB - Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict that during bouts of physical activity, myokine IL-6 fulfills the three main characteristics of a short-term energy allocator: it is secreted from muscle in response to an energy deficit, it liberates somatic energy through lipolysis and it enhances muscular energy uptake and transiently downregulates immune function. We then extend this model of energy allocation beyond myokine IL-6 to reinterpret the roles that IL-6 plays in chronic inflammation, as well as during COVID-19-associated hyperinflammation and multiorgan failure.Interleukin 6 is a pleiotropic cytokine that can be pro- or anti-inflammatory, depending on the metabolic context. Kistner et al. propose that these context-dependent effects are due to its adaptive role for short-term energy allocation, particularly during physical activity.

KW - HUMAN SKELETAL-MUSCLE

KW - EXERCISE-INDUCED INCREASE

KW - MESSENGER-RNA EXPRESSION

KW - FATTY-ACID TRANSPORTERS

KW - ADIPOSE-TISSUE

KW - INSULIN-RESISTANCE

KW - IN-VIVO

KW - GLUCOSE-HOMEOSTASIS

KW - GENE-TRANSCRIPTION

KW - ACUTE-INFLAMMATION

U2 - 10.1038/s42255-022-00538-4

DO - 10.1038/s42255-022-00538-4

M3 - Review

C2 - 35210610

VL - 4

SP - 170

EP - 179

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

IS - 2

ER -