RESUMEN
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to increase due in part to the obesity epidemic and to environmental exposures to metabolism disrupting chemicals. A single gavage exposure of male mice to Aroclor 1260 (Ar1260), an environmentally relevant mixture of non-dioxin-like polychlorinated biphenyls (PCBs), resulted in steatohepatitis and altered RNA modifications in selenocysteine tRNA 34 weeks post-exposure. Unbiased approaches identified the liver proteome, selenoproteins, and levels of 25 metals. Ar1260 altered the abundance of 128 proteins. Enrichment analysis of the liver Ar1260 proteome included glutathione metabolism and translation of selenoproteins. Hepatic glutathione peroxidase 4 (GPX4) and Selenoprotein O (SELENOO) were increased and Selenoprotein F (SELENOF), Selenoprotein S (SELENOS), Selenium binding protein 2 (SELENBP2) were decreased with Ar1260 exposure. Increased copper, selenium (Se), and zinc and reduced iron levels were detected. These data demonstrate that Ar1260 exposure alters the (seleno)proteome, Se, and metals in MASLD-associated pathways.
Asunto(s)
Arocloros , Hígado Graso , Selenio , Masculino , Ratones , Animales , Proteoma/metabolismo , Glutatión Peroxidasa/metabolismo , Selenoproteínas/genética , Selenoproteínas/metabolismo , Hígado/metabolismoRESUMEN
Cardiovascular health is influenced by dietary composition and the western diet is composed of varying types/amounts of fat. Conjugated linoleic acid (cLA) is an abundant dietary unsaturated fatty acid associated with health benefits but its biological signaling is not well understood. Nitrite is enriched in vegetables within the diet and can impact signaling of unsaturated fatty acids; however, its role on cLA signaling is not well understood. Elucidating how nitrite may impact the biological signaling of cLA is important due to the dietary consumption of both cLA and nitrite in the western diet. Since co-administration of cLA and nitrite results in cardioprotection during myocardial infarction (MI), it was hypothesized that cLA and nitrite may affect cardiac mitochondrial respiratory function and complex activity in MI. C57BL/6J mice were treated with cLA and nitrite for either 10 or 13days, where MI was induced on day 3. Following treatment, respiration and complex activity were measured. Among the major findings of this study, cLA treatment (10days) decreases state 3 respiration in vivo. Following MI, nitrite alone and in combination with cLA attenuates increased state 3 respiration and decreases hydrogen peroxide levels. Further, nitrite and cLA co-treatment attenuates increased complex III activity after MI. These results suggest that cLA, nitrite and the combination significantly alter cardiac mitochondrial respiratory and electron transport chain activity in vivo and following MI. Overall, the daily consumption of cLA and nitrite in the diet can have diverse cardiovascular implications, some of which occur at the mitochondrial level.
Asunto(s)
Cardiotónicos/uso terapéutico , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácidos Linoleicos Conjugados/uso terapéutico , Mitocondrias Cardíacas/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Nitrito de Sodio/uso terapéutico , Animales , Cardiotónicos/administración & dosificación , Ecocardiografía , Transporte de Electrón , Complejo I de Transporte de Electrón/metabolismo , Complejo II de Transporte de Electrones/metabolismo , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Complejo III de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Corazón/diagnóstico por imagen , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/metabolismo , Ácidos Linoleicos Conjugados/administración & dosificación , Masculino , Ratones Endogámicos C57BL , Mitocondrias Cardíacas/enzimología , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Daño por Reperfusión Miocárdica/diagnóstico por imagen , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/metabolismo , Factores de Acoplamiento de la Fosforilación Oxidativa/metabolismo , Estrés OxidativoRESUMEN
Conjugated linoleic acid (cLA) is a commercially available weight-loss supplement that is not currently regulated by the U.S. FDA. Numerous studies suggest that cLA mediates protection against diseases including cancer, diabetes, atherosclerosis, immune function, and obesity. Based upon these reports, it was hypothesized that supplementation with cLA would improve heart function in aged wild-type (WT) mice. At 10 months of age, mice were treated with cLA, nitrite, or the combination of the two. Echocardiograms revealed that cardiac function was decreased in aged compared to young WT mice, as determined by percentage of fractional shortening. Also, contrary to the hypothesis, mice that received cLA (6-week treatment) had significantly worse cardiac function compared to controls. This effect was attenuated when mice were cotreated with cLA and nitrite. Taken together, these results suggest that cLA-mediated cardiac injury can be circumvented by nitrite supplementation in a murine model of aging.