Tocotrienols reach the brain and play roles in the attenuation of body weight gain and improvement of cognitive function in high-fat diet-treated mice

Abstract

Obesity induces severe disorders such as type 2 diabetes and cardiovascular events, and the number of people with obesity is increasing all over the world. Furthermore, it is possible that obesity increases the risk of cognitive dysfunction via the acceleration of oxidative damage. Tocotrienols, which are part of the vitamin E family, have antioxidant and anti-obesity effects. However, the effects of tocotrienols on high-fat diet-treated mice have not been completely elucidated. In this study, we assessed changes in body weight, spatial reference memory acquisition, liver lipid droplet size, blood brain barrier-related protein expressions and antioxidative defense systems in high-fat diet-treated mice in the presence or absence of tocotrienols. The results showed that tocotrienols significantly inhibited body weight gain and lipid droplet synthesis. Although the amount was very small, it was confirmed that tocotrienols surely reached the brain in the perfused brain. Treatment with tocotrienols was tended to improve cognitive function in the control mice. However, tocotrienols did not modulate blood brain barrierrelated protein expressions or antioxidative defense systems. These results indicate that treatment with tocotrienols could be effective for the prevention of obesity and cognitive dysfunction. Further extended research is needed to elucidate the relationship between anti-obesity and antioxidant effects of tocotrienols, especially in the brain.

Relationship between Cognitive Dysfunction and Age-Related Variability in Oxidative Markers in Isolated Mitochondria of Alzheimer’s Disease Transgenic Mouse Brains

“…The fall time in the rota-rod test tends to be body-weight-dependent. In our previous study, obese mice fell faster than age-matched controls, and a negative correlation between body weight and fall time was observed [ 28 ]. In this study, the mean body weights of the AD mice at each age were lower than those of the age-matched controls, despite being fed ad libitum (control 3-month-old (3 M), 22.44 g; control 6-month-old (6 M), 30.8 g; Control 20-month-old (20 M), 29.18 g; AD 3 M, 18.6 g; AD 6 M, 20.4 g; AD 20 M, 24.2 g).…”

Tocotrienols Attenuate White Adipose Tissue Accumulation and Improve Serum Cholesterol Concentration in High-Fat Diet-Treated Mice

“…As obesity raises the risk of several diseases, such as type-2 diabetes, cardiovascular disease, and atherosclerosis, the prevention of obesity is very important [ 21 , 22 , 23 ]. It has been reported that T3s have an anti-obesity effect in HFD-treated mice [ 9 , 10 , 11 ]. However, the underlying mechanism of this effect has been unclear.…”

“…Previously, it was reported that T3s inhibit HFD-induced hepatic lipid droplet accumulation [ 11 ]. To reveal the effects of T3s on serum lipid metabolism, cholesterol concentrations in serum were measured.…”

“…Understandably, treatment with T3s significantly increased tissue T3 levels. It was previously reported that HFD accumulates lipid droplets in the liver and that T3s inhibit it [ 11 ]. In this study, some serum hepatic damage parameters were measured.…”

“…Tocotrienols (T3s) are vitamin E (VE) homologs whose most notable biological function is as antioxidants [ 7 , 8 ]. It has been reported that T3s significantly suppress body weight gain in high-fat diet (HFD)-treated mice and inhibit liver lipid droplet accumulation [ 9 , 10 , 11 ]. However, the detailed mechanisms of these effects are still unclear.…”