{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:54:20Z","timestamp":1788785660022,"version":"build-2803163510"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,7,29]]},"abstract":"<jats:p>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\u2013 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 \u03b12-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.<\/jats:p>","DOI":"10.1126\/sciadv.abm7355","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T17:58:43Z","timestamp":1659117523000},"source":"Crossref","is-referenced-by-count":27,"title":["Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3908-127X","authenticated-orcid":true,"given":"Carlos Kiyoshi","family":"Katashima","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, S\u00e3o Paulo 13484-350, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-4630","authenticated-orcid":true,"given":"Thayana","family":"de Oliveira Micheletti","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas (UNICAMP), Limeira, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2269-7000","authenticated-orcid":true,"given":"Renata Rosseto","family":"Braga","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, S\u00e3o Paulo 13484-350, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Stellzer","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, S\u00e3o Paulo 13484-350, Brazil."},{"name":"Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Limeira, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8285-7766","authenticated-orcid":true,"given":"Ludger J. 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