Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism.

Autor: Katashima CK; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil., de Oliveira Micheletti T; Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Braga RR; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil., Gaspar RS; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil.; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Goeminne LJE; Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Moura-Assis A; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Crisol BM; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil., Brícola RS; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil., Silva VRR; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil., de Oliveira Ramos C; Laboratory of Nutritional Genomic, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil., da Rocha AL; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Pretol, São Paulo, Brazil.; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Tavares MR; Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Simabuco FM; Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Matheus VA; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Buscaratti L; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Marques-Souza H; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Pazos P; Department of Physiology, Research Center of Molecular Medicine and Chronic Diseases (CIMUS) and CIBER Fisiopatología Obesidad y Nutrición (CB 06/03), Instituto de Salud Carlos III (ISCIII, Ministerio de Economía y Competitividad (MINECO), University of Santiago de Compostela, Santiago de Compostela 15782, Spain., Gonzalez-Touceda D; Department of Physiology, Research Center of Molecular Medicine and Chronic Diseases (CIMUS) and CIBER Fisiopatología Obesidad y Nutrición (CB 06/03), Instituto de Salud Carlos III (ISCIII, Ministerio de Economía y Competitividad (MINECO), University of Santiago de Compostela, Santiago de Compostela 15782, Spain., Tovar S; Department of Physiology, Research Center of Molecular Medicine and Chronic Diseases (CIMUS) and CIBER Fisiopatología Obesidad y Nutrición (CB 06/03), Instituto de Salud Carlos III (ISCIII, Ministerio de Economía y Competitividad (MINECO), University of Santiago de Compostela, Santiago de Compostela 15782, Spain., Del Carmen García M; Department of Physiology, Research Center of Molecular Medicine and Chronic Diseases (CIMUS) and CIBER Fisiopatología Obesidad y Nutrición (CB 06/03), Instituto de Salud Carlos III (ISCIII, Ministerio de Economía y Competitividad (MINECO), University of Santiago de Compostela, Santiago de Compostela 15782, Spain., Neto JCR; Immunometabolism Research Group, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, Brazil., Curi R; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, Brazil.; Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, São Paulo 01506-000, Brazil., Hirabara SM; Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, São Paulo 01506-000, Brazil., Brum PC; School of Physical Education and Sport, University of São Paulo (USP), São Paulo 05508-030, Brazil., Prada PO; Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., de Moura LP; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil.; CEPECE-Center of Research in Sport Sciences, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil., Pauli JR; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil.; CEPECE-Center of Research in Sport Sciences, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil., da Silva ASR; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Pretol, São Paulo, Brazil.; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Cintra DE; Laboratory of Nutritional Genomic, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil., Velloso LA; Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil., Ropelle ER; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil.; Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.; CEPECE-Center of Research in Sport Sciences, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Jul 29; Vol. 8 (30), pp. eabm7355. Date of Electronic Publication: 2022 Jul 29.
DOI: 10.1126/sciadv.abm7355
Abstrakt: 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.
Databáze: MEDLINE