Effects Of Dietary Energy And Methionine Restriction On Lipid Metabolism And Oxidative Stress In Mice

High dietary fat levels bring damages to the balance of body redox status and lipid metabolism, which leads to increased oxidative stress and fat accumulation in the long term. Studies have confirmed that high fat diet with 80% methionine restriction can significantly decrease fat accumulation, which provides a potential new method to control obesity. This study is aimed at exploring effects of methionine restriction with high fat diet on lipid metabolism and redox status in mice, and comparing its effect to that of caloric restriction diet, in order to provide some information for appropriate levels of methionine restriction in diet.In this study, 100 male C57BL/6J mice were randomly divided into five groups: methionine-restricted group 1(MR1: methionine restricted by 80%, high fat level), methionine-restricted group 2(MR2: methionine restricted by 40%, high fat level), control group(C: normal methionine concentration, high fat level), calorie-restricted group 2(CR2: normal methionine concentration, middle fat level), calorie-restricted group 1(CR1: normal methionine concentration, low fat level). Respectively, at the age of 9 weeks and 30 weeks, CLAMS system was used to monitor the oxygen consumption, heat production, activities and respiratory quotients of mice in each group. After mice execution, indices about lipid metabolism and oxidative stress in mice blood, lipid metabolism, oxidative stress in liver and gastrocnemius, blood glucose and glycogen were assayed. And relative genes expression in mice liver, adipose tissue and gastrocnemius were examined. The results are as follows:In the indirect calorimetry analysis, it is showed accompanying the increasing fat content in the diet, mice fed normal high fat diet demonstrated remarkable reduction in oxygen consumption, heat production, activities and respiratory quotient. However, the introduction of methionine restriction in high fat diet significantly improved the level of oxygen consumption, heat production and activities(P<0.05), in which at age of 9 weeks mice MR2 group expressed higher values than MR1 group while vice versa in age 30 weeks. In groups of CR1, CR2 and C, following the increase of fat content in diet, blood glucose, plasma TG, TC, ROS, leptin and hepatic TG, TC, ROS, MDA gradually augmented, along with a gradually decrease of antioxidant enzymes such as CAT, SOD, GSH-Px in blood, CAT, SOD in liver and gastrocnemius among CR1, CR2 and C groups(P<0.05). Compared to groups C and CR2, group CR1 demonstrated a significantly down regulation in lipid synthesis-related genes but a remarkable up regulation in lipid oxidation gene in mice liver in age 30 weeks. In mice fed with methionine restricted high fat diet, it was found that group MR1 and MR2 showed a decrease of TG、TC、ROS、leptin in plasma, a reduction of TG、TC、ROS、MDA in liver but an increase of CAT、SOD、TAOC levels in blood, liver and gastrocnemius when compared to group C. Also, a rise of adiponectin and FGF21 level in blood and a significantly down regulation in lipid synthesis-related genes but a remarkable up regulation in lipid oxidation gene in mice liver were also observed in the methionine restriction introduced groups(P<0.05). MR also decrease the level of blood glucose and increase glycogen level in mice fed high fat diet. MR intervention made indices of mice feeding high fat diet return to the similar or higher level of that of CR1 group. At the age of 9 weeks, MR2 group expressed higher statistics in energy consumption, FGF21, antioxidant capacity and lower statistics in TG, TC, blood glucose than MR1 group but vice versa at the age of 30 weeks.This study further demonstrates that either in the short-term or in the long-term feeding, different levels of methionine restriction can effectively increase energy consumption, counteract the negative effects of abnormal lipid metabolism and restore the body’s antioxidant capacity in mice, which can prevent the occurring of obesity. Both the caloric restriction of 4% fat in the diet and methionine restriction can effectively inhibit the occurrence of obesity, but these two methods may affect in different mechanisms. The 40% methionine restriction leads to better parameters in antioxidant ability, TG, TC and blood glucose than that of caloric restriction of 4% fat in the diet in age 9 weeks, while in age 30 weeks, the 80% methionine restriction leads to these parameters better than that of caloric restriction of 4% fat in the diet. And it is found the appropriet methionine restriction level to mice before maturity is higher than that to the mice after maturity.