Cover Story Current Issue

Glucose is a ubiquitous and essential source of energy for all living organisms. Although mammals have evolved ways to convert other nutritional molecules to ATP, the preference for dietary glucose appears to be preserved. In rodents, the immediate detection of ingested glucose potently reinforces intake, hierarchically organizing behaviors towards glucose-yielding substances, and away from other types of food including other sugars. Taste is the primary sense linked to nutrient selection. Until recently, it was thought that most mammalian species utilize a single broadly tuned receptor to detect all simple sugars. Indeed, this “sweet” receptor, which comprises a heterodimer of the T1R2 and T1R3 proteins, binds multiple natural sugars (e.g., glucose, fructose, sucrose, maltose), as well as various other chemicals that yield little to no energy (e.g., low calorie sweeteners, sugar alcohols) and some d-amino acids. The neural signal originating from the sweet receptor is hardwired into brain circuits that drive eating and drinking behaviors, but it is an unreliable indicator of nutrient quality and quantity.

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Current Issue

Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis

Timothy M. Kistner, Beckey Trinh, Karl Mfeketo, Gerrit van Hall, ... Helga Ellingsgaard

Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis

Background/Purpose

During exercise, myokine interleukin 6 (IL-6) plays a variety of metabolic roles including acting as a muscular energy sensor and liberating somatic energy stores. While the effects of IL-6 are relatively well-defined during exercise, its role in muscular metabolism during exercise recovery in humans has not been addressed.

Methods

To test whether myokine IL-6 allocates fat and glucose towards muscle, we conducted a randomized double-blind trial with 30 men (Age: 25.2 ± 3 yrs. BMI: 23.0 ± 1.5 kg/m2) where participants exercised at a moderate intensity for 2 h and received either tocilizumab to block IL-6 activity, or placebo. Continuous infusions of isotopically labeled palmitate, glucose, and glycerol paired with blood, breath, and muscle samples were used to measure muscle-specific metabolism.

Results

IL-6 blockade did not affect exercise performance, substrate utilization, or glucose, fatty acid and glycerol kinetics during exercise. During recovery, IL-6 blockade decreased the appearance of oral glucose and lowered the insulin response to a glucose drink. Despite this difference in glucose and insulin, the rate of post-exercise glycogen resynthesis before and after the ingestion of glucose was not altered between groups. Although IL-6 blockade did not affect lipolysis during exercise, it attenuated the accumulation of esterified oleate in muscle during recovery before the glucose drink was given. Furthermore, IL-6 blockade attenuated IL-1RA production in recovery but did not alter IL-10 secretion.

Conclusion

Together, these results imply that during recovery from moderate-intensity exercise, myokine IL-6 primarily regulates fatty acid metabolism within muscle and leaves glucose metabolism largely unaffected.

Articles in Press

Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis

Timothy M. Kistner, Beckey Trinh, Karl Mfeketo, Gerrit van Hall, ... Helga Ellingsgaard

Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis

Background/Purpose

During exercise, myokine interleukin 6 (IL-6) plays a variety of metabolic roles including acting as a muscular energy sensor and liberating somatic energy stores. While the effects of IL-6 are relatively well-defined during exercise, its role in muscular metabolism during exercise recovery in humans has not been addressed.

Methods

To test whether myokine IL-6 allocates fat and glucose towards muscle, we conducted a randomized double-blind trial with 30 men (Age: 25.2 ± 3 yrs. BMI: 23.0 ± 1.5 kg/m2) where participants exercised at a moderate intensity for 2 h and received either tocilizumab to block IL-6 activity, or placebo. Continuous infusions of isotopically labeled palmitate, glucose, and glycerol paired with blood, breath, and muscle samples were used to measure muscle-specific metabolism.

Results

IL-6 blockade did not affect exercise performance, substrate utilization, or glucose, fatty acid and glycerol kinetics during exercise. During recovery, IL-6 blockade decreased the appearance of oral glucose and lowered the insulin response to a glucose drink. Despite this difference in glucose and insulin, the rate of post-exercise glycogen resynthesis before and after the ingestion of glucose was not altered between groups. Although IL-6 blockade did not affect lipolysis during exercise, it attenuated the accumulation of esterified oleate in muscle during recovery before the glucose drink was given. Furthermore, IL-6 blockade attenuated IL-1RA production in recovery but did not alter IL-10 secretion.

Conclusion

Together, these results imply that during recovery from moderate-intensity exercise, myokine IL-6 primarily regulates fatty acid metabolism within muscle and leaves glucose metabolism largely unaffected.

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