Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism-Reference-Cited by-同舟云学术

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

Published:2022-07-29 Issue:30 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Katashima Carlos Kiyoshi¹^ORCID,de Oliveira Micheletti Thayana²^ORCID,Braga Renata Rosseto¹^ORCID,Gaspar Rodrigo Stellzer¹³,Goeminne Ludger J. E.⁴^ORCID,Moura-Assis Alexandre³^ORCID,Crisol Barbara Moreira¹,Brícola Rafael S.¹^ORCID,Silva Vagner Ramon R.¹,de Oliveira Ramos Camila⁵,da Rocha Alisson L.⁶⁷^ORCID,Tavares Mariana Rosolen⁸^ORCID,Simabuco Fernando Moreira⁸^ORCID,Matheus Valquiria Aparecida⁹^ORCID,Buscaratti Lucas¹⁰^ORCID,Marques-Souza Henrique¹⁰^ORCID,Pazos Patricia¹¹^ORCID,Gonzalez-Touceda David¹¹^ORCID,Tovar Sulay¹¹^ORCID,del Carmen García María¹¹^ORCID,Neto Jose Cesar Rosa¹²^ORCID,Curi Rui¹³¹⁴^ORCID,Hirabara Sandro Massao¹⁴^ORCID,Brum Patrícia Chakur¹⁵^ORCID,Prada Patrícia Oliveira²^ORCID,de Moura Leandro P.¹¹⁶,Pauli José Rodrigo¹¹⁶,da Silva Adelino S. R.⁶⁷^ORCID,Cintra Dennys Esper⁵^ORCID,Velloso Licio A.²³,Ropelle Eduardo Rochete¹²³¹⁶^ORCID

Affiliation:

1. Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeria, São Paulo 13484-350, Brazil.

2. Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.

3. Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.

4. Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

5. Laboratory of Nutritional Genomic, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil.

6. Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Pretol, São Paulo, Brazil.

7. School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

8. Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.

9. Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.

10. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.

11. 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.

12. Immunometabolism Research Group, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, Brazil.

13. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, Brazil.

14. Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, São Paulo 01506-000, Brazil.

15. School of Physical Education and Sport, University of São Paulo (USP), São Paulo 05508-030, Brazil.

16. CEPECE—Center of Research in Sport Sciences, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo 13484-350, Brazil.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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