Search

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.

Benefits of exercise have been documented for many diseases with a chronic progression, including obesity, diabetes mellitus, cardiovascular diseases, neurodegenerative diseases, certain types of cancers, and overall mortality. Low-grade systemic inflammation is a key component of these pathologies and it has been demonstrated that can be prevented by performing regularly physical exercise. The aim of this study was to examine the effect of lipopolysaccharide (LPS)-induced inflammation on glucose and insulin tolerance, exercise performance, production of urinary neopterin and striatal neurotransmitters levels in adult male C57BL/6 mice. Increased blood glucose clearance and insulin sensitivity were observed after a single administration of glucose (2 g/kg, p.o.) or insulin (0.5 U/kg, i.p.). However, the repeated injection of LPS (0.33 mg/kg/day, i.p.) decreased glucose tolerance and increase urinary neopterin levels, pointing to systemic inflammation. In parallel to the urinary-increased neopterin, it was observed a significant reduction in the striatal dopamine levels and an increase in the serotonin/dopamine ratio. While a single LPS injection (0.33 mg/kg, i.p.) showed impaired performance in the incremental loading test (10 m/min, with 2 m/min increment every 3 min, at 9% grade), a moderate physical exercise protocol (treadmill for three weeks; 5 sessions/week; up to 50 min/day) prevented the exacerbation of immune system activation and preserved mitochondrial activity in skeletal muscle from mice with continuous LPS infusion (infusion pumps: 0.83 mg/kg/day, i.p.). In conclusion, the peripheral-induced inflammation elicited metabolic alterations that provoked impairment in striatal dopamine metabolism. The moderate exercise prevented the increase of urinary neopterin and preserved mitochondrial activity under LPS-induced inflammatory conditions.