The nuclear receptor Nr2f6 represses skeletal muscle oxidative metabolism and force production
Dimitrius Santiago Passos Simões Fróes Guimarães, Ninon Melany Flores Barrios, André Gustavo de Oliveira, David Rizo-Roca, Maxence Jollet, Jonathon A. B. Smith, Thiago Reis Araujo, Marcos Vinicius da Cruz, Emilio Marconato, Sandro Massao Hirabara, André Schwambach Vieira, Anna Krook, Juleen R....
Dimitrius Santiago Passos Simões Fróes Guimarães, Ninon Melany Flores Barrios, André Gustavo de Oliveira, David Rizo-Roca, Maxence Jollet, Jonathon A. B. Smith, Thiago Reis Araujo, Marcos Vinicius da Cruz, Emilio Marconato, Sandro Massao Hirabara, André Schwambach Vieira, Anna Krook, Juleen R. Zierath, Leonardo dos Reis Silveira
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Agradecimentos: We would like to appreciate the technical support of Ann-Marie Petterson. This work was supported by São Paulo Research Foundation (FAPESP) (thematic projects and scholarships: 2016/23008-5, 2017/24795-3, 2021/07411-2, 2018-20581-1, 2017/24851-0), by the Karolinska Institutet Grants...
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Agradecimentos: We would like to appreciate the technical support of Ann-Marie Petterson. This work was supported by São Paulo Research Foundation (FAPESP) (thematic projects and scholarships: 2016/23008-5, 2017/24795-3, 2021/07411-2, 2018-20581-1, 2017/24851-0), by the Karolinska Institutet Grants with support from Swedish Diabetes Foundation (DIA2021-645), Swedish Research Council for Sport Science (P2019-0140 and P2020-0064), and the Swedish Research Council (2015-00165). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001 and by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Abstract: The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. However, the transcriptional control of both processes by nuclear receptors (NR) remains...
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Abstract: The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. However, the transcriptional control of both processes by nuclear receptors (NR) remains underexplored. Nr2f6 is an orphan NR and a key regulator of metabolism and differentiation. Nonetheless, its role in muscle biology remains elusive. Here, we report, for the first time, the effects of Nr2f6 modulation in skeletal muscle in vivo and in vitro . Depletion of Nr2f6 increased myocyte’s oxidative capacity and sharply attenuated lipid-induced cell death, which was associated with direct derepression of uncoupling protein 3 and PGC-1a promoters’ transactivation. Conversely, Nr2f6 overexpression in the tibialis anterior induced atrophy and hypoplasia, accompanied by impairment of force production and the establishment of a molecular signature of inflammation, and a decrease in genes involved in oxidative metabolism and contraction. Additionally, global transcriptomics showed that Nr2f6 upregulated core components of the cell division machinery and repressed myogenesis genes, thus decoupling myoblast proliferation from differentiation. Collectively, our findings define a novel role for Nr2f6 as a molecular transducer maintaining the balance between skeletal muscle contractile function and oxidative capacity, with implications for metabolic diseases and myopathies treatment
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FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP
2016/23008-5; 2017/24795-3; 2017/24851-0; 2018-20581-1; 2021/07411-2
COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES
001
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ
Aberto
The nuclear receptor Nr2f6 represses skeletal muscle oxidative metabolism and force production
Dimitrius Santiago Passos Simões Fróes Guimarães, Ninon Melany Flores Barrios, André Gustavo de Oliveira, David Rizo-Roca, Maxence Jollet, Jonathon A. B. Smith, Thiago Reis Araujo, Marcos Vinicius da Cruz, Emilio Marconato, Sandro Massao Hirabara, André Schwambach Vieira, Anna Krook, Juleen R....
Dimitrius Santiago Passos Simões Fróes Guimarães, Ninon Melany Flores Barrios, André Gustavo de Oliveira, David Rizo-Roca, Maxence Jollet, Jonathon A. B. Smith, Thiago Reis Araujo, Marcos Vinicius da Cruz, Emilio Marconato, Sandro Massao Hirabara, André Schwambach Vieira, Anna Krook, Juleen R. Zierath, Leonardo dos Reis Silveira
The nuclear receptor Nr2f6 represses skeletal muscle oxidative metabolism and force production
Dimitrius Santiago Passos Simões Fróes Guimarães, Ninon Melany Flores Barrios, André Gustavo de Oliveira, David Rizo-Roca, Maxence Jollet, Jonathon A. B. Smith, Thiago Reis Araujo, Marcos Vinicius da Cruz, Emilio Marconato, Sandro Massao Hirabara, André Schwambach Vieira, Anna Krook, Juleen R....
Dimitrius Santiago Passos Simões Fróes Guimarães, Ninon Melany Flores Barrios, André Gustavo de Oliveira, David Rizo-Roca, Maxence Jollet, Jonathon A. B. Smith, Thiago Reis Araujo, Marcos Vinicius da Cruz, Emilio Marconato, Sandro Massao Hirabara, André Schwambach Vieira, Anna Krook, Juleen R. Zierath, Leonardo dos Reis Silveira
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bioRxiv May 2023 |