Swimming training and caffeine supplementation protects against metabolic syndrome-induced NF-kB activation and cognitive deficits in rats

Metabolic syndrome (MS) is a disorder that increasingly affects the world population, mainly due to changes in lifestyle and dietary habits. In this regard, both physical exercise and caffeine are low-cost and easily accessible therapies that separately have shown positive effects against metabolic disorders. Therefore, we hypothesized that physical exercise combined with caffeine could have a synergistic effect in the treatment of MS, risk factors and cognitive deficits. Animals were divided into eight groups and received fructose (15% w/v) or vehicle for 10 weeks. Swimming training and caffeine (6 mg/kg) started four weeks after fructose administration. Trained animals presented decreased body weight and visceral fat mass and increased soleus weight compared with fructose-treated animals. Caffeine supplementation also prevented the gain of visceral fat mass induced by fructose. Furthermore, both treatments reverted fructose-induced decrease in glucose clearance over time and fructose-induced increase in 4-HNE and NF-κB immunoreactivity. Physical training also improved the lipidic profile in fructose-treated animals (HDL, LDL, and triglycerides), improved short-term, long-term, and localization memory, and reverted the fructose-induced deficit in short-term memory. Physical training also increased NRF2 immunoreactivity per se. Considering that physical training and caffeine reverted some of the damages induced by fructose it is plausible to consider these treatments as an alternative, non-pharmacological and low-cost therapies to help reduce MS-associated risk factors, however, combined treatments did not show additive effects as hypothesized.