Effect And Mechanism Of Procyanidin On Lipoclasis In Normal And Obese Mice

Procyanidins, a class of phenolic compounds, are widely available in natural.Since they can produce anthocyanin if are heated in acid medium, so named that. They have a broad range of biological activities. As a research focus in and abroad in recent years, procyanidins are widely used in healthy products, medicine, cosmetics and other fields. Epidemiological data and in vivo studies suggest that procyanidins have beneficial properties against adipocyte-related pathologies such as obesity, insulin resistance and diabetes. However, their exact effects and the mechanisms involved remain obscure. Some researches provide evidence that obesity is associated with abnormally elevated JNK activity, predominantly provided by JNK1. Importantly, the absence of JNK1 results in substantial protection from obesity-induced insulin resistance.The present research aimed at exploring the effect and mechanism of grape seed procyanidin extract (GSPE) on the lipoclasis of mice. To provide a theoretical proof for further illustrate the regulation of anti-obesity by GSPE. Kunming mice were the study subjects. GSPE were given to the normal and obese mice by gavage daily. The body weight, the concentrations of serum T-CHO, TG, HDL-C, LDL-C, glucose-tolerance and insulin-tolerance were measured; Lipase activity in mice liver and adipose tissues was measured by Lipase Activity Test Kit. Real-time PCR and western blotting were applied to detect the genes mRNA and proteins expression levels of two major transcription factors PPARγ,C/EBPαas well as HSL and FAS mRNA were measured by Real-time PCR. We also explore the relationship between anti-obesity of GSPE and JNK signal pathway. The main results were summarized as follows:1. Fed with normal diet, in different doses GSPE treated groups, the body weight gain of mice decreased. In the low dose GSPE treated group, the concentration of T-CHO in serum decreased significantly (P<0.05), the concentration of HDL-C was increased significantly (P<0.05). In the middle dose GSPE group, the concentration of TG, T-CHO and LDL-C in serum decreased significantly (P<0.05), the concentration of HDL-C was increased extremely significantly (P<0.01), and in the high dose GSPE group, the concentration of TG, T-CHO, LDL-C in serum decreased extremely significantly (P<0.01), the concentration of HDL-C was increased extremely significantly (P<0.01). The glucose-tolerance and insulin-tolerance were not affected by GSPE. With regard to the expression level of FAS, C/EBPα, and PPARγmRNA, GSPE-treated can be down-regulated. But the expression of HSL was not affected.2. Fed with high-fat diet, GSPE can slow the weight gain. Measured the glucose-tolerance and insulin-tolerance show that the trend of high blood glucose was improved. The changes of genes expression are the same with normal diet treated group. But the expression level of FAS and PPARγare decreased extremely significantly (P<0.01) in the high dose GSPE treated group, HSL expression was increased extremely significantly (P<0.01). GSPE can increase the lipase activity in mice liver and adipose tissues. It can be seen that GSPE can decrease the fat deposition of high-diet treated mice and it plays an important role in preventing the production of obesity.3. Feed the high-diet induced obese mice in normal diet, the results show that, GSPE can reduce the body weight of mice and show the does-independent manner. The concentrations of T-CHO, TG and LDL-C in blood serum decreased significantly (P<0.05) or extremely significantly (P<0.01) in different GSPE-treated groups. But the concentration of HDL-C increased significantly (P<0.05) or extremely significantly (P<0.01). Meanwhile, GSPE can improve the trend of high blood glucose in obese mice. The mice in the control group show some insulin resistance after inject insulin, but the mice in the GSPE-treated groups can improve such condition. The relative expression levels of C/EBPα,FAS and PPARγwere significantly down-regulated (P<0.05) or extremely significantly down-regulated (P<0.01), while the expression level of HSL was up-regulated (P<0.05 and P<0.01 respectively) in different GSPE-treated groups compared with the control group. Based on these results, we concluded that the grape seed procyanidin extract can inhibit the fat deposition of obese mice, and it plays a beneficial role in treating obesity.4. The research has proved that GSPE can inhibit the fat deposition of mica and show the does-independent manner, we chose the optimal dose and add the agonist and inhibitor of JNK pathway to treat the obese mice. The results shown that GSPE can decrease the body weight, the serum lipid level, improve the high blood glucose and resistance of insulin, it also up-regulates the lipolysis and down-regulate the lipid synthesis genes and protein expression. It is interesting that, Compared with the GSPE treated group, SP600125 inhibit the JNK pathway can enhance the effect of GSPE, while anisomycin can have the opposite effect. In a word, GSPE can inhibit the fat deposition of obese mice through inhibiting the JNK pathway.