Browsing by Author "Valero-Breton, Mayalen"

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    Angiotensin-(1-7) improves skeletal muscle regeneration
    (2023) Valero-Breton, Mayalen; Tacchi, Franco; Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Cabello-Verrugio, Claudio
    Skeletal muscle possesses regenerative potential via satellite cells, compromised in muscular dystrophies leading to fibrosis and fat infiltration. Angiotensin II (Ang-II) is commonly associated with pathological states. In contrast, Angiotensin (1-7) [Ang-(1-7)] counters Ang-II, acting via the Mas receptor. While Ang-II affects skeletal muscle regeneration, the influence of Ang-(1-7) remains to be elucidated. Therefore, this study aims to investigate the role of Ang-(17) in skeletal muscle regeneration. C2C12 cells were differentiated in the absence or presence of 10 nM of Ang-(1-7). The diameter of myotubes and protein levels of myogenin and myosin heavy chain (MHC) were determined. C57BL/6 WT male mice 16-18 weeks old) were randomly assigned to injury-vehicle, injury-Ang-(1-7), and control groups. Ang-(1-7) was administered via osmotic pumps, and muscle injury was induced by injecting barium chloride to assess muscle regeneration through histological analyses. Moreover, embryonic myosin (eMHC) and myogenin protein levels were evaluated. C2C12 myotubes incubated with Ang-(1-7) showed larger diameters than the untreated group and increased myogenin and MHC protein levels during differentiation. Ang-(1-7) administration enhances regeneration by promoting a larger diameter of new muscle fibers. Furthermore, higher numbers of eMHC (+) fibers were observed in the injured-Ang-(1-7), which also had a larger diameter. Moreover, eMHC and myogenin protein levels were elevated, supporting enhanced regeneration due to Ang-(1-7) administration. Ang-(1-7) effectively promotes differentiation in vitro and improves muscle regeneration in the context of injuries, with potential implications for treating muscle-related disorders.
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    Bile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers
    (2022) Abrigo, Johanna; Olguin, Hugo; Gutierrez, Danae; Tacchi, Franco; Arrese, Marco; Cabrera, Daniel; Valero-Breton, Mayalen; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, Claudio
    Cholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5(-/-) mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5(-/-) mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.
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    Metabolic flexibility to lipid during exercise is not associated with metabolic health outcomes in individuals without obesity
    (Nature Research, 2024) Fernández Verdejo, Rodrigo; Gutierrez-Pino, Juan; Hayes Ortiz, Thomas Emilio; Zbinden Foncea, Hermann; Cabello Verrugio, Claudio Alejandro; Valero-Breton, Mayalen; Tunon-Suarez, Mauro; Vargas-Foitzick, Ronald; Galgani Fuentes, José
    A low metabolic flexibility to lipid (MetF-lip) in skeletal muscle may promote ectopic lipid accumulation, thus inducing metabolic disturbances. We aimed to determine the association between MetF-lip in skeletal muscle and metabolic health outcomes in individuals without obesity. We also explored the association between MetF-lip and the inflammatory signaling pathway in skeletal muscle. This was a cross-sectional study in 17 individuals aged (median [IQR]) 55.4 [48.6, 58.5] years, with a BMI of 24.4 [22.6, 26.0] kg/m(2). MetF-lip was assessed as the increase in relative lipid oxidation during a single exercise session (similar to 50% VO(2)max, 2 hours), quantified as the drop in whole-body respiratory exchange ratio (Delta RER = RER at 2 hours - maximum RER attained). HOMA-IR, metabolic syndrome z-score, fat percentage, trunk-to-appendicular fat, and VO(2)max were included as metabolic health outcomes. The abundance of proteins of the inflammatory pathway was analyzed in resting muscle. Acute exercise progressively increased relative lipid oxidation (Delta RER = -0.04 [-0.08, -0.02]). MetF-lip was not associated with any metabolic health outcome but correlated inversely with p-p38(Thr180/Tyr182) in muscle. A low MetF-lip in skeletal muscle does not seem a major determinant of metabolic disturbances but associates with a partial activation of the inflammatory signaling in individuals without obesity.