限量饮食对黄曲霉素B_1-DNA加合物生成的影响

本实验用黄曲霉毒素Ｂ１（ＡｆｌａｔｏｘｉｎＢ１，ＡＦＢ１）作为致癌物代表，研究限量饮食（Ｆｏｏｄｒｅｓｔｒｉｃｔｉｏｎ，ＦＲ）对雄性Ｆ３４４大鼠和Ｂ６Ｃ３Ｆ１小鼠代谢活化ＡＦＢ１的影响。ＡＦＢ１－ＤＮＡ加合物（ＡＤＡ）作为ＡＦＢ１代谢活化的生物指标。结果显示ＦＲ降低大鼠和小鼠对ＡＦＢ１的代谢活化，ＡＤＡ的生成在大鼠和小鼠中分别减少４３％和３１％。ＡＤＡ的两种主要加合物的生成、分布和清除以及它们与ＡＦＢ１致癌作用的关系也作了讨论。

限量饮食对小鼠体内黄曲霉素B1及苯（α）芘DNA加合物的影响

限量饮食对小鼠体内黄曲霉素Ｂ１及苯（α）芘ＤＮＡ加合物的影响陈雯，吴中亮，周明武，张桥（广州医学院化学致癌研究所广州５１０１８２中山医科大学卫生学院，美国国家毒理研究中心）限量饮食（Ｄｉｅｔａｒｙｒｅｓｔｒｉｃｔｉｏｎ，ＤＲ）对化学诱癌有抑制作用，可...

限量饮食对致癌物活化代谢及DNA断裂的影响

目的：研究限量饮食（ＤＲ）对小鼠肝代谢活化致癌物以及致癌物导致的ＤＮＡ链断裂程度的影响。方法：用３２Ｐ后标记和高效液相色谱法测定致癌物ＤＮＡ主要加合物生成量；用随机寡核甘酸引物合成法（ＲＯＰＳ）测定ＤＮＡ链断裂程度；用体外代谢酶活性测定法检测有关代谢酶的活性。结果：①限量饮食减少小鼠肝中黄曲霉毒素Ｂ１（ＡＦＢ１）和２乙基氨基芴（２ＡＡＦ）ＤＮＡ加合物（ＡＦＣ８ｄＧ）的生成，同时也减少致癌物导致的ＤＮＡ链断裂；限量饮食增加苯并［ａ］芘（ＢａＰ）ＤＮＡ加合物（ＢａＰＮ２ｄＧ）和６硝基苯甲萘（６ＮＣ）ＤＮＡ总加合物的生成，也增加致癌物导致的ＤＮＡ链断裂。②在小鼠肝中，致癌物ＤＮＡ加合物的生成量与致癌物导致的ＤＮＡ链断裂程度密切相关；③限量饮食诱导某些与致癌物代谢有关的酶。结论：限量饮食特异地改变小鼠肝代谢酶的活性继而影响致癌物的代谢活化，这种作用在致癌过程的起始阶段可能起着重要的作用。

限量饮食对化学致癌物-DNA加合物生成的影响

用黄曲霉毒素Ｂ１（ＡＦＢ１）、苯并（ａ）芘（ＢａＰ）和２－乙基氨基芴（２－ＡＡＦ）作为致癌物代表，研究限量饮食（Ｄｉｅｔａｒｙｒｅｓｔｒｉｃｔｉｏｎ，ＤＲ）对雄性Ｆ３４４大鼠和Ｂ６Ｃ３Ｆ１小鼠代谢活化致癌物的影响。以几种致癌物主要的ＤＮＡ加合物作为代谢活化的生物指标。结果显示：限量饮食降低大鼠和小鼠的体重，降低ＡＦＢ１－ＤＮＡ加合物（ＡＤＡ）的生成，增加ＡＦＢ１－谷胱甘肽结合物（ＡＦＢ１－ＳＧ）的生成，增加ＢａＰ－ＤＮＡ加合物（Ｂｐ－Ｎ２－ｄＧ）的生成，但对２－ＡＡＦ－ＤＮＡ加合物（ＡＦ－Ｃ８－ｄＧ）的作用有双重性，染毒后２４，４８小时ＡＦ－Ｃ８－ｄＧ在两组动物肝中无差别，而７２小时后则明显降低ＡＦ－Ｃ８－ｄＧ的生成。结果说明：对于不同的致癌物，ＤＲ有选择性改变代谢酶活性的作用。

小鼠限量对小鼠免疫功能、肠道菌群及寿命的影响

采用饮食限量法，将昆明小鼠分三组：自由进食、八份进食和半量进食的小鼠分别进行了免疫功能、肠道菌群与寿命的观察。结果显示：八份饱进食组小鼠寿命最长，２年全部存活（１００％），自由进食组次之（３３％），半量进食组只到１８个月就全部死亡。在免疫的检测中发现ＡＮＡＥ＋数及Ｍφ吞噬试验，八份饱进食组最高，自由进食组次之，半量进食组最低，相差显著或非常显著。在肠道需厌Ｏ２菌的检测中，结果显示：克雷伯氏菌、双岐杆菌、乳杆菌八份饱进食组明显的高于其自由进食组（ｐ＜００５）和半量进食组（ｐ＜００１），提示长寿小鼠免疫功能的增强及部分细菌的增加和适量的饮食限量有着密切的关系。

Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction

AIM： To characterise the effect of energy restriction （ER） on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium. METHODS： Liver metabolomic profile of lean and obese C57BI/6J mice （n = 10/group） were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet （whey ＋ Ca）. The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS： ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey ＋ Ca diet significantly decreased blood glucose （P 〈 0.001） and serum insulin （P 〈 0.01）. In hepatic lipid species the biggest reduction was in the level of triacylglycerols and cerarnides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey ＋ Ca ER group （P 〈 0.001, vs obese）. ER on whey ＋ Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic cerarnides （P 〈 0.001, vs obese; P 〉 0.05, vs lean）. These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway rnetabolites. CONCLUSION： ER-induced changes on hepatic rnetabolornic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.

Effect of Linguizhugan decoction on hyperlipidemia rats with intermittent fasting

OBJECTIVE:To explore the effect of Linguizhugan decoction on hyperlipidemia rats with caloric restriction.METHODS:The hyperlipidemia model of rat was induced by high fat diet for 8 weeks.After the model was established,26 rats were randomly divided into 4 groups:the control group(n=6),the model group(n=6),the intermittent fasting(IF) group(n= 8),and the IF and herbal medicine(IFH) group(n= 6).IF group was applied intermittent fasting every other day.The IFH group was given Linguizhugan decoction every day and intermittent fasting every other day.Blood samples were taken at the end of 16 weeks,and serum ghrelin and lipid was tested.RESULTS:Serum ghrelin in the IF group significantly increased(P<0.01).Serum ghrelin in IFH group was lower than the IF group(P<0.05),but higher than the model group(P<0.01).CONCLUSION:Linguizhugan decoction may play a part in regulation of energy and appetite in hyperlipidemia rats with IF.

Effect of a combination of calorie-restriction therapy and Lingguizhugan decoction on levels of fasting blood lipid and inflammatory cytokines in a high-fat diet induced hyperlipidemia rat model

OBJECTIVE:To combine calorie-restriction therapy(CRT) with Traditional Chinese Medicine(TCM) using Lingguizhugan Decoction and note the effects on expression of inflammatory cytokines[tumor necrosis factor(TNF)-α,high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6]in high-fat-diet induced hyperlipidemia in rats.METHODS:Forty rats were divided randomly and equally into four groups:control group A(regular feeding for 5 weeks);model group B(high-fat diet for 5 weeks),calorie-limited group C(high-fat diet for 5 weeks) and TCM calorie-limit group D(high-fat diet for 5 weeks).After modeling,groups C and D were fasted for 3 days:group C with simple fasting,and group D with TCM fasting.The motion as well as changes in color,body weight,food intake,plasma lipids[low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol,total cholesterol(TC) and triglyceride(TG) along with TNF-α,hs-CRP and IL-6]were measured before and after intervention.RESULTS:Modeled rats were established after five weeks.After 3 days of fasting,compared with group B,blood lipid levels(TG,TC,LDL-C) of groups C and D decreased dramatically.Those of group D decreased more obviously than those of group C.However,the values of TNF-α,hs-CRP and IL-6 showed no obvious difference between each of the three treatment groups.CONCLUSION:CRT can reduce fasting blood lipid levels in rats,but not by reducing the levels of inflammatory cytokines.

Intermittent protein restriction protects isletβcells and improves glucose homeostasis in diabetic mice

Diabetes is caused by the interplay between genetics and environmental factors, tightly linked to lifestyle and dietary patterns. In this study, we explored the effectiveness of intermittent protein restriction(IPR)in diabetes control. IPR drastically reduced hyperglycemia in both streptozotocin-treated and leptin receptor-deficient db/db mouse models. IPR improved the number, proliferation, and function of β cells in pancreatic islets. IPR reduced glucose production in the liver and elevated insulin signaling in the skeletal muscle. IPR elevated serum level of FGF21, and deletion of the Fgf21 gene in the liver abrogated the hypoglycemic effect of IPR without affecting β cells. IPR caused less lipid accumulation and damage in the liver than that caused by continuous protein restriction in streptozotocin-treated mice. Single-cell RNA sequencing using mouse islets revealed that IPR reversed diabetes-associated β cell reduction and immune cell accumulation. As IPR is not based on calorie restriction and is highly effective in glycemic control and β cell protection, it has promising translational potential in the future.