RESUMO
Evidence has shown that caffeine administration reduces pro-inflammatory biomarkers, delaying fatigue and improving endurance performance. This study examined the effects of caffeine administration on the expression of inflammatory-, adenosine receptor- (the targets of caffeine), epigenetic-, and oxidative metabolism-linked genes in the vastus lateralis muscle of mice submitted to lipopolysaccharide (LPS)-induced inflammation. We showed that caffeine pre-treatment before LPS administration reduced the expression of Il1b, Il6, and Tnfa, and increased Il10 and Il13. The negative modulation of the inflammatory response induced by caffeine involved the reduction of inflammasome components, Asc and Casp1, promoting an anti-inflammatory scenario. Caffeine treatment per se promoted the upregulation of adenosinergic receptors, Adora1 and Adora2A, an effect that was counterbalanced by LPS. Moreover, there was observed a marked Adora2A promoter hypermethylation, which could represent a compensatory response towards the increased Adora2A expression. Though caffeine administration did not alter DNA methylation patterns, the expression of DNA demethylating enzymes, Tet1 and Tet2, was increased in mice receiving Caffeine+LPS, when compared with the basal condition. Finally, caffeine administration attenuated the LPS-induced catabolic state, by rescuing basal levels of Ampk expression. Altogether, the anti-inflammatory effects of caffeine in the muscle can be mediated by modifications on the epigenetic landscape.
RESUMO
Obesity and metabolic disorders are increasing worldwide and are associated with brain atrophy and dysfunction, which are risk factors for late-onset dementia and Alzheimer's disease. Epidemiological studies demonstrated that changes in lifestyle, including the frequent practice of physical exercise are able to prevent and treat not only obesity/metabolic disorders, but also to improve cognitive function and dementia. Several biochemical pathways and epigenetic mechanisms have been proposed to understand the beneficial effects of physical exercise on cognition. This manuscript revised central ongoing research on epigenetic mechanisms induced by exercise and the beneficial effects on obesity-associated cognitive decline, highlighting potential mechanistic mediators.