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beta-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight
dc.contributor.author | Hidalgo Gutiérrez, Agustín | |
dc.contributor.author | Barriocanal Casado, Eliana | |
dc.contributor.author | Díaz Casado, María Elena | |
dc.contributor.author | González García, Pilar | |
dc.contributor.author | Acuña Castroviejo, Darío | |
dc.contributor.author | López García, Luis Carlos | |
dc.date.accessioned | 2021-11-23T07:44:49Z | |
dc.date.available | 2021-11-23T07:44:49Z | |
dc.date.issued | 2021-10-13 | |
dc.identifier.citation | Hidalgo-Gutiérrez, A... [et al.]. beta -RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight. Biomedicines 2021, 9, 1457. [https://doi.org/10.3390/biomedicines9101457] | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/71673 | |
dc.description | This work was supported by grants from Ministerio de Ciencia e Innovacion, Spain, and the ERDF (grant number RTI2018-093503-B-100); from the Muscular Dystrophy Association (MDA602322); from the Junta de Andalucia (grant number P20_00134); from the University of Granada (grant reference "UNETE," UCE-PP2017-06); and by EPIC-XS, project number 823839, funded by the Horizon 2020 program of the European Union. P.G.-G. is a "FPU fellow" from the Ministerio de Universidades, Spain. M.E.D.-C. is supported by the Muscular Dystrophy Association. E.B.-C. is supported by the Junta de Andalucia. A.H.-G. was partially supported by the "FPU program" and the research program from the University of Granada. | es_ES |
dc.description.abstract | Primary mitochondrial diseases are caused by mutations in mitochondrial or nuclear genes, leading to the abnormal function of specific mitochondrial pathways. Mitochondrial dysfunction is also a secondary event in more common pathophysiological conditions, such as obesity and metabolic syndrome. In both cases, the improvement and management of mitochondrial homeostasis remain challenging. Here, we show that beta-resorcylic acid (beta-RA), which is a natural phenolic compound, competed in vivo with 4-hydroxybenzoic acid, which is the natural precursor of coenzyme Q biosynthesis. This led to a decrease in demethoxyubiquinone, which is an intermediate metabolite of CoQ biosynthesis that is abnormally accumulated in Coq9(R239X) mice. As a consequence, beta-RA rescued the phenotype of Coq9(R239X) mice, which is a model of primary mitochondrial encephalopathy. Moreover, we observed that long-term treatment with beta-RA also reduced the size and content of the white adipose tissue (WAT) that is normally accumulated during aging in wild-type mice, leading to the prevention of hepatic steatosis and an increase in survival at the elderly stage of life. The reduction in WAT content was due to a decrease in adipogenesis, an adaptation of the mitochondrial proteome in the kidneys, and stimulation of glycolysis and acetyl-CoA metabolism. Therefore, our results demonstrate that beta-RA acted through different cellular mechanisms, with effects on mitochondrial metabolism; as such, it may be used for the treatment of primary coenzyme Q deficiency, overweight, and hepatic steatosis. | es_ES |
dc.description.sponsorship | Spanish Government | es_ES |
dc.description.sponsorship | European Commission RTI2018-093503-B-100 | es_ES |
dc.description.sponsorship | Muscular Dystrophy Association MDA602322 | es_ES |
dc.description.sponsorship | Junta de Andalucia P20_00134 | es_ES |
dc.description.sponsorship | University of Granada UCE-PP2017-06 | es_ES |
dc.description.sponsorship | EPIC-XS - Horizon 2020 program of the European Union 823839 | es_ES |
dc.description.sponsorship | Muscular Dystrophy Association | es_ES |
dc.description.sponsorship | Junta de Andalucia | es_ES |
dc.description.sponsorship | Spanish Government | es_ES |
dc.description.sponsorship | University of Granada | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | Atribución 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Mitochondrial disease | es_ES |
dc.subject | Encephalopathy | es_ES |
dc.subject | Astrogliosis | es_ES |
dc.subject | Spongiosis | es_ES |
dc.subject | Obesity | es_ES |
dc.subject | White adipose tissue | es_ES |
dc.subject | Mitochondrial proteome | es_ES |
dc.subject | 3T3-L1 | es_ES |
dc.subject | Mouse model | es_ES |
dc.subject | Hepatic steatosis | es_ES |
dc.title | beta-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight | es_ES |
dc.type | journal article | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/823839 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.3390/biomedicines9101457 | |
dc.type.hasVersion | VoR | es_ES |
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