RT Journal Article
T1 β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight.
A1 Hidalgo-Gutiérrez, Agustín
A1 Barriocanal-Casado, Eliana
A1 Díaz-Casado, María Elena
A1 González-García, Pilar
A1 Zenezini Chiozzi, Riccardo
A1 Acuña-Castroviejo, Darío
A1 López, Luis Carlos
K1 3T3-L1
K1 astrogliosis
K1 encephalopathy
K1 hepatic steatosis
K1 mitochondrial disease
K1 mitochondrial proteome
K1 mouse model
K1 obesity
K1 spongiosis
K1 white adipose tissue
AB 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 (β-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 Coq9R239X mice. As a consequence, β-RA rescued the phenotype of Coq9R239X mice, which is a model of primary mitochondrial encephalopathy. Moreover, we observed that long-term treatment with β-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 β-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.
SN 2227-9059
YR 2021
FD 2021-10-13
LK https://hdl.handle.net/10668/27931
UL https://hdl.handle.net/10668/27931
LA en
DS RISalud
RD Apr 12, 2025