RES can also play a role in metabolic disease prevention. Metabolic diseases include epidemics such as obesity and diabetes. A study showed that when RES was given orally to mice it activated a protein in the Sirtuin family, which henceforth activated another protein for mitochondrial function. This same study demonstrated that fasting insulin levels were significantly decreased after RES, suggesting an insulin sensitization. Increased insulin sensitivity is important because obesity is directly correlated with poor insulin sensitivity. Furthermore, the study proved that RES increases the association of the SIRT1 enzyme with energy expenditure, which therefore led to a reduction in weight gain. The following set of graphs illustrates the results from this study.
RES increases insulin sensitivity and the association of the SIRT1 gene with energy expenditure
(A) Average glucose, insulin, and lipid levels in HF-fed C57Bl/6J mice treated with or without RES (HF + R400) for 16 weeks. N = 8–10 animals/group.
(B) Eight week-old male KKAy mice were treated with HF diet or HF diet plus RSV at a dose of 400 mpk (HF+R400) for 8 weeks. N = 5 animals/group. OGTT was performed, and the AUCs are shown in the inset bar graph (B). Values represent means ± SEM. * = P < 0.05.
Another study similar to the above had three groups of mice, one group fed a high calorie diet, a second group with a normal diet, and the third group was given RES along with a high calorie diet. The results showed that when the high calorie fed mice reached old age (114 weeks), greater than 50% had died compared to less than 33% of the high calorie mice receiving resveratrol. Results also showed that mice receiving RES had lower plasma levels of insulin, glucose and insulin-like growth factor (IGF) 1– all of which are markers for the onset of diabetes in humans if elevated. After the mice died, researchers examined their hearts and found that inflammation and deterioration were incredibly less for the RES supplemented group and normal diet group as compared to the high calorie only mice. It turns out that the mechanism of these biological effects is connected to the activation of the enzyme known as SIRT1.
This mechanism was proven by the fact that levels of PGC-1alpha were three-fold lower in the resveratrol group than in the high calorie group, which is what is expected to happen when SIRT1 is being activated by RES. Research has shown that calorie restrictions (CR) of at least 30-40% lengthens productive lifespan in numerous animals. This incredible effect is due to the activation of the SIRT1 enzyme. However, living a life with calorie restrictions is very arduous and in some cases burdensome. Therefore, researchers have looked upon other ways to activate the SIRT1 enzyme. RES is one such compound that can activate the SIRT1 and mimic the effects of calorie restriction. Basically, when RES enters cells, the enzyme SIRT1 is activated. This activation of SIRT1 creates new mitochondria in muscle and other tissues.
As a result, the new mitochondria increase basal metabolic rate, which therefore mimics the effects of a CR diet. Mitochondria burn sugar to release energy. However, they are similar to coal fired power plants in that they pollute. The mitochondria belch chemicals known as free radicals which damage DNA, among other things. Eventually, the radicals destroy the mitochondria, thereby creating less efficient mitochondria that spew even more free radicals. This cascade is one of the major causes of aging. Fortunately, RES has the ability to create new mitochondria. This is important because new mitochondria are more efficient and produce less free radicals.
There is a very severe microvascular ailment known as diabetic nephropathy, which is one of the primary causes of the final stage of renal disease. Research has shown that oxidative stress is a major cause of this ailment. A study performed on diabetic mice treated with RES showed that the RES greatly eased renal distress and oxidative stress. This protective effect of RES is most likely due to its antioxidant properties.