@misc{10481/71673,
year = {2021},
month = {10},
url = {http://hdl.handle.net/10481/71673},
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.},
organization = {Spanish Government},
organization = {European Commission	RTI2018-093503-B-100},
organization = {Muscular Dystrophy Association	MDA602322},
organization = {Junta de Andalucia	P20_00134},
organization = {University of Granada	UCE-PP2017-06},
organization = {EPIC-XS - Horizon 2020 program of the European Union	823839},
organization = {Muscular Dystrophy Association},
organization = {Junta de Andalucia},
organization = {Spanish Government},
organization = {University of Granada},
publisher = {MDPI},
keywords = {Mitochondrial disease},
keywords = {Encephalopathy},
keywords = {Astrogliosis},
keywords = {Spongiosis},
keywords = {Obesity},
keywords = {White adipose tissue},
keywords = {Mitochondrial proteome},
keywords = {3T3-L1},
keywords = {Mouse model},
keywords = {Hepatic steatosis},
title = {beta-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight},
doi = {10.3390/biomedicines9101457},
author = {Hidalgo Gutiérrez, Agustín and Barriocanal Casado, Eliana and Díaz Casado, María Elena and González García, Pilar and Acuña Castroviejo, Darío and López García, Luis Carlos},
}