ArticleScience advances2022
Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Exercise elicits mitonuclear protein imbalance and UPRJournal of physiology and biochemistry · 2026Article
- Hypothalamus-Peripheral Organ Crosstalk in Energy Metabolism: A Bidirectional Regulatory Network.Endocrinology and metabolism (Seoul, Korea) · 2026Review
- Rapid Metabolic and Behavioral Maladaptations Following Short-Term Obesogenic Diet Withdrawal During Postweaning Development in Male Wistar Rats.Brain and behavior · 2026Article
- Association between occupational sedentary behavior and metabolic syndrome and related diseases in males: A cross-sectional study.PloS one · 2026Article
- Evaluating current status of network pharmacology for herbal medicine focusing on identifying mechanisms and therapeutic effects.Journal of advanced research · 2025Article
- GLP-1/GLP-1R axis: from metabolism (obesity and T2DM) to immunity.Open biology · 2025Review
- Dietary protein restriction regulates skeletal muscle fiber metabolic characteristics associated with the FGF21-ERK1/2 pathway.iScience · 2024Article
- IL-6 and diabetic kidney disease.Frontiers in immunology · 2024Review
- Muscle-derived extracellular vesicles mediate crosstalk between skeletal muscle and other organs.Frontiers in physiology · 2024Review
- Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.Drug design, development and therapy · 2024Article
- Exercise metabolism and adaptation in skeletal muscle.Nature reviews. Molecular cell biology · 2023Review
- Exercise-induced hypothalamic neuroplasticity: Implications for energy and glucose metabolism.Molecular metabolism · 2023Review
- Functional role of skeletal muscle-derived interleukin-6 and its effects on lipid metabolism.Frontiers in physiology · 2023Review
- Acute exercise reduces feeding by activating IL-6/Tubby axis in the mouse hypothalamus.Frontiers in physiology · 2022Article
Corrections and comments
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Authors and funding
31 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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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