AI Article Synopsis

  • Hypothalamic interleukin-6 (IL6) activates the ERK1/2 pathway in the ventromedial hypothalamus, which promotes fatty acid oxidation in mouse skeletal muscle via AMPK/ACC signaling.
  • Bioinformatics analysis links the IL6/ERK1/2 pathway to fatty acid metabolism-related genes in both mice and humans, indicating its broad metabolic control.
  • The study shows that the α2-adrenergic pathway is necessary for IL6's effect on muscle metabolism, as blocking the IL6 receptor in the VMH disrupts exercise-induced fatty acid oxidation.

Article Abstract

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation- and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337767PMC
http://dx.doi.org/10.1126/sciadv.abm7355DOI Listing

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