Abstract
GPR120 and GPR40 were recently reported as omega-3 (ω3) receptors with anti-inflammatory properties. Physical exercise could increase the expression of these receptors in the liver, improving hepatic metabolism in obesity and type 2 diabetes. Our aim was to investigate GPR120/40 in the liver of lean and obese mice after acute or chronic physical exercise, with or without the supplementation of ω3 rich flaxseed oil (FS), as well as assess the impact of exercise and FS on insulin signaling and inflammation. Mice were fed a high-fat diet (HF) for 4 weeks to induce obesity and subsequently subjected to exercise with or without FS, or FS alone. Insulin signaling, inflammatory markers and GPR120/40 and related cascades were measured. Chronic, but not acute, exercise and FS increased GPR120, but not GPR40, activating β-arrestin-2 and decreasing the inflammatory response, as well as reducing fat depots in liver and adipose tissue. Exercise or a source of ω3 led to a higher tolerance to fatigue and an increased running distance and speed. The combination of physical exercise and ω3 food sources could provide a new strategy against obesity through the modulation of hepatic GPR120 and an increase in exercise performance.
Link to Full Text
Key Points
Low-grade inflammation is considered one of the most relevant mechanisms of obesity and related disturbances. It is well documented that both ω3 supplementation and physical exercise have anti-inflammatory properties in obesity as well as in improving the action of insulin. This study focused on the association between Dietary ω3 and exercise in obesity and showed that chronic exercise and ω3 have a synergistic effect on the hepatic levels and anti-inflammatory signaling of the recently deorphanized GPR120, and improve metabolic and molecular parameters in obese mice. Given the potential of both exercise and ω3 in improving health state in obesity and insulin resistance/type 2 diabetes mellitus, it was hypothesized that acute and chronic exercise could increase insulin sensitivity and exercise performance, decrease inflammation and importantly increase the expression of GPR120 and GPR40 in the liver and that these effects could be enhanced by ω3 supplementation (FS oil). GPR120 but not GPR40 seems to be positively modulated by exercise and FS, decreasing the hepatic inflammation induced by increased fat consumption. The mechanisms by which physical exercise modulates GPR120 expression have not been investigated. No effect of FS oil alone on insulin action was shown. In summary, the results show that acute physical exercise is not involved in the modulation of GPR120 or GRP40 expression in the liver of lean mice. Chronic exercise increased levels of GPR120, although not GPR40, in the liver of obese mice, as did an FS oil supplement. The insulin signaling was not ameliorated by interventions; however, the inflammatory tonus in the liver was improved. FS oil contributed to increase the performance of running mice, improving the aerobic power.