The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

Background: The higher consumption of fat and sugar are associated with obesity development and its related diseases such as non-alcoholic fatty liver disease (NAFLD). Lycopene is an antioxidant whose protective potential on fatty liver degeneration has been investigated. The aim of this study was to present the therapeutic effects of lycopene on NAFLD related to the obesity induced by a hypercaloric diet. Methods: Wistar rats were distributed in two groups: Control (Co, n = 12) and hypercaloric (Ob, n = 12). After 20 weeks, the animals were redistributed into the control group (Co, n = 6), control group supplemented with lycopene (Co+Ly, n = 6), obese group (Ob, n = 6), and obese group supplemented with lycopene (Ob+Ly, n = 6). Ob groups also received water + sucrose (25%). Animals received lycopene solution (10 mg/kg/day) or vehicle (corn oil) via gavage for 10 weeks. Results: Animals which consumed the hypercaloric diet had higher adiposity index, increased fasting blood glucose, hepatic and blood triglycerides, and also presented in the liver macro and microvesicular steatosis, besides elevated levels of tumor necrosis factor-α (TNF-α). Lycopene has shown therapeutic effects on blood and hepatic lipids, increased high-density lipoprotein cholesterol (HDL), mitigated TNF-α, and malondialdehyde (MDA) and further improved the hepatic antioxidant capacity. Conclusion: Lycopene shows therapeutic potential to NAFLD.

The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as dyslipidemia, hypertension, and cardiovascular disease. The aim of this study was to evaluate the association between dyslipidemia and cardiac dysfunction induced by western diet consumption. Wistar rats were randomly divided into two experimental groups and fed ad libitum for 20 weeks with a control diet (Control, n = 12) or a high-sugar and high-fat diet (HSF, n = 12). The HSF group also received water + sucrose (25%). Evaluations included feed and caloric intake; body weight; plasma glucose; insulin; uric acid; HOMA-IR; lipid profile: [total cholesterol (T-chol), high-density lipoprotein (HDL), non-HDL Chol, triglycerides (TG)]; systolic blood pressure, and Doppler echocardiographic. Compared to the control group, animals that consumed the HSF diet presented higher weight gain, caloric intake, feed efficiency, insulin, HOMA-IR, and glucose levels, and lipid profile impairment (higher TG, T-chol, non-HDL chol and lower HDL). HSF diet was also associated with atrial-ventricular structural impairment and systolic-diastolic dysfunction. Positive correlation was also found among the following parameters: insulin versus estimated LV mass (r = 0.90, p = 0.001); non-HDL versus deceleration time (r = 0.46, p = 0.02); TG versus deceleration time (r = 0.50, p = 0.01). In summary, our results suggest cardiac remodeling lead by western diet is associated with metabolic parameters.

The system redox imbalance is one of the pathways related to obesity-related cardiac dysfunction. Lycopene is considered one of the best antioxidants. The aim of this study was to test if the tomato-oleoresin would be able to recovery cardiac function by improving β-adrenergic response due its antioxidant effect. A total of 40 animals were randomly divided into two experimental groups to receive either the control diet (Control, n = 20) or a high sugar-fat diet (HSF, n = 20) for 20 weeks. Once cardiac dysfunction was detected by echocardiogram in the HSF group, animals were re- divided to begin the treatment with Tomato-oleoresin or vehicle, performing four groups: Control (n = 6); (Control + Ly, n = 6); HSF (n = 6) and (HSF + Ly, n = 6). Tomato oleoresin (10 mg lycopene/kg body weight (BW) per day) was given orally every morning for a 10-week period. The analysis included nutritional and plasma biochemical parameters, systolic blood pressure, oxidative parameters in plasma, heart, and cardiac analyses in vivo and in vitro. A comparison among the groups was performed by two-way analysis of variance (ANOVA). Results: The HSF diet was able to induce obesity, insulin-resistance, cardiac dysfunction, and oxidative damage. However, the tomato-oleoresin supplementation improved insulin-resistance, cardiac remodeling, and dysfunction by improving the β-adrenergic response. It is possible to conclude that tomato-oleoresin is able to reduce the oxidative damage by improving the system’s β-adrenergic response, thus recovering cardiac function.