高脂饮食诱导的C57BL/6J肥胖小鼠脂肪组织RIP140基因表达水平的研究(英文)

目的:探讨高脂饮食致肥胖小鼠脂肪组织RIP140mRNA表达水平的变化及其与胰岛素抵抗的关系。方法:将C57BL/6J雄性小鼠随机分为正常饮食(NFD)组、高脂饮食(HFD)组分别喂养14周后,测量两组小鼠体重,以NFD组小鼠体重作为对照,选取HFD组中体重大于对照组小鼠平均体重20%的小鼠作为肥胖组小鼠。对照组和肥胖组小鼠取血测甘油三酯(TG)、总胆固醇(TC)、空腹血糖(FBG)、空腹胰岛素水平(FIns),计算稳态模型胰岛素抵抗指数(HOMA-IR);采用RT-PCR技术检测两组小鼠附睾脂肪组织RIP140 mRNA的表达水平,并进行统计学分析。结果:HDF组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠TG、TC、FBG、FIns(P0.05),HOMA-IR(P0.01)均明显高于对照组;肥胖组小鼠脂肪组织RIP140 mRNA的表达高于对照组,差异具有统计学意义(P0.05);相关分析显示小鼠脂肪组织RIP140 mRNA表达水平与TG水平呈正相关(r=0.536,P0.05),与胰岛素抵抗指数呈正相关(r=0.465,P0.05),而与TC、FBG、FIns水平相关分析无统计学意义(P0.05)。结论:高脂饮食诱导的肥胖小鼠脂肪组织RIP140 mRNA表达增加,并与胰岛素抵抗程度呈正相关。     

二氢杨梅素对高脂饮食诱导的小鼠肥胖的影响及其机制

目的:观察二氢杨梅素(DHM)对高脂饮食诱导小鼠肥胖的影响,并探讨其作用机制是否与促进WAT棕色化有关。方法:60只c57bl/6j小鼠随机分为6组(n=10):①正常对照组(ND组):普通饲料喂养、②正常对照+低剂量DHM组(ND+L-DHM组):普通饲料喂养同时用低剂量DHM(125 mg/(kg·d))处理、③正常对照+高剂量DHM组(ND+H-DHM组):普通饲料喂养同时用高剂量DHM(250 mg/(kg·d))处理、④高脂饮食组(HFD):高脂饲料喂养、⑤高脂饮食+低剂量DHM组(HFD+L-DHM组):高脂饲料喂养同时用低剂量DHM处理、⑥高脂饮食+高剂量DHM组(HFD+H-DHM组):高脂饲料喂养同时用高剂量DHM处理。16周后小鼠空腹过夜,取血测空腹血糖和血脂,随后处死动物,测体长,算出Lee's指数;取肩胛下、腹股沟和附睾处脂肪组织称重后,甲醛固定、HE染色观察脂肪细胞大小,免疫组化检测解偶联蛋白1(UCP1)的表达;实验期间每4周测一次小鼠体重。结果:与ND组相比较,HFD组小鼠体重显著升高,提示肥胖小鼠模型复制成功。此外,HFD组小鼠体脂重量、脂肪细胞直径、Lee's指数和血糖显著增加、脂肪细胞UCP1的表达升高;使用L-DHM和H-DHM处理HFD小鼠后,体脂重量、脂肪细胞直径、Lee's指数和血糖等指标显著逆转,而脂肪细胞UCP1的表达升高更为显著;但L-DHM和H-DHM对正常小鼠上述指标无显著影响。结论:二氢杨梅素抑制高脂饮食诱导的小鼠肥胖,其机制可能与促进WAT棕色化有关。     

不同强度电针对肥胖大鼠脂肪组织炎症相关因子的影响

探讨不同强度电针对肥胖大鼠脂肪组织核因子-κBp65(NF-κBp65)、单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)的作用差异.将SD大鼠随机分为普通饮食组、高脂饮食组、5 V电针组、2.5 V电针组,除普通饮食组外其余各组大鼠均饲以高脂饲料.取"足三里"、"三阴交"穴,不同强度电针治疗14 d后,用蛋白质印迹技术(Western blot)检测肥胖大鼠附睾脂肪组织NF-κBp65的表达,酶联免疫吸附法(ELISA)检测肥胖大鼠附睾脂肪组织MCP-1、TNF-α的含量.研究发现两电针组肥胖大鼠体重、Lee’s指数、脂肪组织中NF-κBp65表达、MCP-1和TNF-α含量较高脂饮食组显著降低(P<0.01),5 V电针组较2.5 V电针组下降效果更为明显(P<0.01,P<0.05).结果表明电针可改善肥胖脂肪组织炎症反应状态,减轻肥胖大鼠体重,且5 V电针组效果优于2.5 V电针组.     

下丘脑Orexin 对肥胖大鼠能量代谢的影响

目的:探讨下丘脑注射OXR-1选择性受体拮抗剂ACT-335827对肥胖大鼠代谢的效果。方法:通过高脂饮食建立肥胖大鼠模型,采用CODA 8通道高通量非侵入性血压系统(EMKA)测量血压;所有脂类都使用商品酶试剂盒和TOSHIBA-40FR全自动分析仪测量;空腹血糖采用葡萄糖氧化酶法;空腹胰岛素采用放射免疫法测定。肥胖大鼠出现代谢紊乱后,给予ACT-335827处理,检测大鼠体重、血压、脂肪、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、游离脂肪酸(NEFA)、瘦素、空腹血糖及空腹胰岛素等的变化。结果:与普通饮食组相比,经过10周高脂饮食,高脂饮食组大鼠体重显著升高(P0.05),给予ACT-335827处理后,普通大鼠的体重、血压、脂肪含量、脂代谢等均无明显变化;与高脂饮食和高脂饮食加生理盐水处理组大鼠比较,高脂饮食加ACT-335827处理组肥胖大鼠的体重显著下降(P0.05),腹部和附睾脂肪含量下降(P0.05),低密度脂蛋白、甘油三酯、总胆固醇、瘦素水平下降(P0.05),空腹血糖及空腹胰岛素也显著降低(P0.05),但血压、肠系膜脂肪和肩胛棕色脂肪、高密度脂蛋白和NEFA无明显变化(P0.05)。结论:ACT-335827对肥胖大鼠的代谢紊乱具有改善作用,对肥胖大鼠有一定的减肥作用。     

不同配方益生菌在高脂饮食诱导小鼠肥胖发生中的差异化作用

【目的】基于肠道微生物与宿主代谢的相互关系,研究不同配方的益生菌对小鼠肥胖的影响。【方法】50只C57BL/6J雄性小鼠随机平均分成10组,分别给予正常饲料、高脂饲料以及高脂饲料加8种不同配方的益生菌产品(50亿CFU/只),所有动物连续喂养9周,每周测量小鼠体重1次。最后一周测定空腹血糖、葡萄糖耐量试验(glucose tolerance test,GTT)、血脂相关指标,称取内脏重量,并留取小鼠盲肠内容物,提取小鼠肠道菌群总DNA,利用16S rDNA测序检测相关细菌含量。【结果】部分益生菌可引起小鼠体重增速加快,而部分益生菌可减缓小鼠肥胖和降低内脏脂肪重量,同时缓解高血脂症。丹尼斯克品牌益生菌配方组小鼠肠道中厚壁菌/拟杆菌比例(F/B)是正常饮食组的22.8倍,Akkermansia muciniphila(Akkermansia)细菌含量几乎为0;而菌拉丁品牌益生菌配方组小鼠F/B比例与正常饲料饮食组类似,Akkermansia含量为0.5%,为正常饮食对照组小鼠的一半左右。【结论】益生菌可影响小鼠体重和代谢,但不同配方的益生菌效果截然相反。特定的益生菌配方对肥胖和高血脂的改善可能是由于其选用的菌株本身的特性以及菌株之间的相互配比能够降低小鼠肠道中F/B比例以及升高Akkermansia的含量所带来的。此研究为进一步开发可改善代谢的益生菌产品提供了参考。     

黄芪水提取物减轻高脂饮食引起的小鼠肥胖

目的:研究黄芪水提取物(Astragalus radix extract,ARE)对高脂饮食(High fat diet,HFD)引起的小鼠肥胖的作用及可能机制。方法:将30只C57 BL/6小鼠随机分为正常喂养组(ND组,n=10)、高脂喂养组(HFD组,n=10)和高脂喂养+黄芪水提取物处理组(ARE组,n=10)。记录三组小鼠体重及食物摄入。在喂养16周时,对小鼠附睾白色脂肪称重,并进行HE染色观察脂肪细胞大小;对小鼠肝脏进行进行HE染色观察肝脏脂肪变性情况。应用ELISA方法检测血清瘦素及脂联素水平。应用Western Blot检测脂肪组织过氧化物酶体增殖物激活受体γ(Peroxisome proliferator activated receptorγ,PPARγ)表达。结果:1与ND组相比,HFD组体重及热量摄入均显著增加,表明肥胖模型建立成功;ARE处理组的体重较HFD组显著下降,但其热量摄入与HFD组相当。2与ND组相比,HFD组白色脂肪组织重量增加、脂肪细胞增大、肝细胞出现显著脂肪变性;ARE处理组上述指标较HFD组明显改善。3与ND组相比,HFD组瘦素水平升高、脂联素水平下降;ARE处理组与HFD组相比,瘦素水平降低、脂联素水平升高。4与ND组相比,HFD组PPARγ表达显著增加,而ARE处理组较HFD组PPARγ表达下降。结论:黄芪水提取物可能通过抑制PPARγ减轻高质饮食引起的肥胖。     

DHA对高脂食物诱导体重增加的保护作用的研究

目的为了探索DHA抑制高脂食物诱导的脂肪增加的机制。方法本研究通过给C57BL/6小鼠饲喂普通食物(C57BL/6 C组),45%高脂食物(C57BL/6 H组)以及45%高脂食物加DHA(每克食物0. 2 g的DHA)(FAD3 C组)和(每克食物0. 4 g的DHA)(FAD3 H组),20周。第19周测定静止代谢率,20周处死动物检测血清瘦素、甘油三酯的浓度,以及白色脂肪组织和褐色脂肪组织中脂肪分化因子和褐色基因的表达。结果研究发现高脂食物导致C57BL/6 H组的体重、体脂、瘦素和甘油三酯最高(P0. 05)。与C57BL/6 H组相比,DHA降低了体重、体脂、瘦素和甘油三酯(P0. 05),并且有剂量依赖性。在白色脂肪中,DHA降低了高脂食物诱导的PPARγ、CEBPα和SREP1c mRNA表达的增加(P0. 05)。与对照组相比,DHA显著增加白色脂肪组织和褐色脂肪组织中脂肪褐色化基因PGC1αmRNA和UCP1 mRNA表达(P0. 05)。结论食物补充DHA通过增加产热基因的表达,增加静止代谢率、降低白色脂肪和褐色脂肪的脂肪分化基因的表达,从而降低高脂食物诱导的体重增加。     

高脂饮食诱导的C57BL／6J肥胖小鼠脂肪组织RIP140基因表达水平的研究

目的：探讨高脂饮食致肥胖小鼠脂肪组织RIP140mRNA表达水平的变化及其与胰岛素抵抗的关系。方法：将C57BL／6J雄性小鼠随机分为正常饮食（NFD）组、高脂饮食（HFD）纽分别喂养14周后,测量两组小鼠体重,以NFD组小鼠体重作为对照,选取HFD组中体重大于对照组小鼠平均体重20％的小鼠作为肥胖组小鼠。对照组和肥胖组小鼠取血测甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FBG）、空腹胰岛素水平（FIns）,计算稳态模型胰岛素抵抗指数（HOMA-IR）;采用RT—PCR技术检测两组小鼠附睾脂肪组织RIP140 mRNA的表达水平,并进行统计学分析。结果：HDF组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠TG、TC、FBG、Fins（P〈0．05）,HOMA-1R（P〈0．01）均明显高于对照组;肥胖组小鼠脂肪组织RIP140mRNA的表达高于对照组,差异具有统计学意义（P〈0．05）;相关分析显示小鼠脂肪组织R1P140 mRNA表达水平与TG水平呈正相关（r=0．536,P〈0．05）,与胰岛素抵抗指数呈正相关（r=0．465,P〈0．05）,而与TC、FBG、Fins水平相关分析无统计学意义（P〉0．05）。结论：高脂饮食诱导的肥胖小鼠脂肪组织RIP140 mRNA表达增加,并与胰岛素抵抗程度呈正相关。     

白藜芦醇对高脂饲养小鼠脂肪组织氧化还原状态及血脂的影响

本研究旨在探索白藜芦醇(RSV)对不同程度肥胖小鼠脂肪氧化应激状态和血脂的影响。高脂日粮(HFD)处理12周的昆明小鼠分为3类:肥胖抵抗(DIO-R)、中体重(Med)和肥胖(DIO),分别饲喂HFD、HFD+0.3 g/kg RSV和HFD+0.6 g/kg RSV日粮18周,并以正常日粮小鼠为对照。结果表明,0.6 g/kg RSV处理可显著降低DIO小鼠体重、腹脂率,显著提高脂肪组织抗氧化能力,改善血脂。0.3 g/kg RSV处理对DIO-R小鼠也有类似趋势,但0.6 g/kg RSV处理引起DIO-R小鼠脂肪组织抗氧化能力下降、血脂紊乱。总之,RSV在不同程度肥胖小鼠具有剂量特异性的氧化应激调控作用。     

高脂饮食对小鼠脂质代谢和leptin基因表达水平的影响

目的建立高脂饮食诱导小鼠肥胖模型,分析高脂饲料对小鼠脂质代谢和leptin基因表达水平的影响。方法用高脂饲料饲喂小鼠,每周定时称重和断尾采血一次,分别测定血清中血糖、胆固醇、甘油三酯、胰岛素和leptin的浓度;5周后,分离、称重小鼠体脂并提取腹部脂肪组织RNA,半定量RT-PCR分析leptin基因表达水平。结果从第2周开始,实验组小鼠体重明显高于对照组小鼠,4周后,体重差异显著（P〈0．05）;血清中血糖、胆固醇、甘油三酯、胰岛素和leptin的含量随体重增加明显增高,4周后,差异显著（P〈0．05）;实验组体脂含量明显高于对照组（P〈0．05）,半定量RT-PCR分析表明,肥胖小鼠脂肪组织leptin基因表达水平高于对照组（P〈0．05）。结论高脂饮食诱导可建立小鼠肥胖模型,并能够引起高胰岛素和高leptin血症,为进一步研究肥胖的发病机制奠定基础。     

Prevention and Reversal of Obesity and Glucose Intolerance in Mice by DHA Derivatives

The n‐3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert hypolipidemic effects and prevent development of obesity and insulin resistance in animals fed high‐fat diets. We sought to determine the efficacy of α‐substituted DHA derivatives as lipid‐lowering, antiobesity, and antidiabetic agents. C57BL/6 mice were given a corn oil‐based high‐fat (35% weight/weight) diet (cHF), or cHF with 1.5% of lipids replaced with α‐methyl DHA ethyl ester (Substance 1), α‐ethyl DHA ethyl ester (Substance 2), α,α‐di‐methyl DHA ethyl ester (Substance 3), or α‐thioethyl DHA ethyl ester (Substance 4) for 4 months. Plasma markers of glucose and lipid metabolism, glucose tolerance, morphology, tissue lipid content, and gene regulation were characterized. The cHF induced obesity, hyperlipidemia, impairment of glucose homeostasis, and adipose tissue inflammation. Except for Substance 3, all other substances prevented weight gain and Substance 2 exerted the strongest effect (63% of cHF‐controls). Glucose intolerance was significantly prevented (～67% of cHF) by both Substance 1 and Substance 2. Moreover, Substance 2 lowered fasting glycemia, plasma insulin, triacylglycerols, and nonesterified fatty acids (73, 9, 47, and 81% of cHF‐controls, respectively). Substance 2 reduced accumulation of lipids in liver and skeletal muscle, as well as adipose tissue inflammation associated with obesity. Substance 2 also induced weight loss in dietary obese mice. In contrast to DHA administered either alone or as a component of the EPA/DHA concentrate (replacing 15% of dietary lipids), Substance 2 also reversed established glucose intolerance in obese mice. Thus, Substance 2 represents a novel compound with a promising potential in the treatment of obesity and associated metabolic disturbances.     

胆汁酸G-蛋白偶联受体激动剂齐墩果酸对高脂饮食小鼠体内糖脂代谢的影响

目的观察胆汁酸G-蛋白偶联受体（Gprotein—coupled receptor for bile acids,TGR5）激动剂齐墩果酸（oleanolic acid,OA）对肥胖小鼠体重及糖、脂代谢的影响,探讨齐墩果酸减轻肥胖小鼠体重的机制。方法建立高脂饮食诱导的肥胖小鼠动物模型,并喂食OA进行干预。动态测定体重及第17周后内脏脂肪、肝脏重量,并进行葡萄糖耐量实验（glucose tolerence test,GTT）;肝脏组织石蜡切片HE染色,光镜观察病理变化;Realtime PCR检测肝脏组织糖代谢相关基因的表达及白色脂肪组织脂肪合成酶（fatty acid synthase,FAS）的表达。结果OA减轻肥胖小鼠的体重、内脏脂肪及肝脏的重量;改善肝脏脂质沉积;增强胰岛素敏感性。OA抑制肝脏内葡萄糖-6-磷酸酶（glucose-6-phosphatase,G6Pc）的表达,并下调肥胖小鼠脂肪组织FAS的mRNA水平的表达。结论TGR5激动剂OA能减少高脂诱导的肥胖小鼠的脂肪堆积,其机制可能与OA能改善肥胖小鼠胰岛素抵抗,减少脂质合成有关。     

Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets — LSO, FO2.5, FO12.5 or FO25 — containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice.     

Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.     

Studies on lipogenesis in vivo. Lipogenesis during extended periods of re-feeding after starvation

1. Lipogenesis was studied in mice re-fed for up to 21 days after starvation. At appropriate times [U-(14)]glucose was given by stomach tube and incorporation of (14)C into various lipid fractions measured. 2. In mice starved for 48hr. and then re-fed for 4 days with a diet containing 1% of corn oil, incorporation of (14)C from [U-(14)C]glucose into liver fatty acids and cholesterol was respectively threefold and eightfold higher than in controls fed ad libitum. The percentages by weight of fatty acids and cholesterol in the liver also increased and reached peaks after 7 days. Both the radioactivity and weights of the fractions returned to control values after 10-14 days' re-feeding. These changes could be diminished by re-feeding the mice with a diet containing 20% of corn oil. Incorporation of (14)C from [U-(14)C]glucose into extrahepatic fatty acids (excluding those of the epididymal fat pads) was not elevated during re-feeding with a diet containing either 1% or 20% of corn oil. However, incorporation of (14)C from [U-(14)C]glucose into the fatty acids of the epididymal fat pads was increased in mice re-fed with either diet, as compared with non-starved controls. 3. Lipogenesis was also studied in mice alternately fed and starved. Mice given a diet containing 1% of corn oil for 6hr./day for 4 weeks lost weight initially and never attained the weight or carcass fat content of controls fed ad libitum. Incorporation of (14)C from dietary [U-(14)C]-glucose into the fatty acids of the epididymal fat pads was elevated threefold in the mice allowed limited access to food, although the incorporation into the remainder of the extrahepatic fatty acids was not different from that found for controls. Mice given a diet containing 20% of corn oil for 6hr./day adapted to the limited feeding regimen quicker and in 4 weeks did attain the weight and carcass fat content of controls. Incorporation of (14)C from [U-(14)C]glucose into the fatty acids of the epididymal fat pads and the remainder of the extrahepatic fatty acids was respectively fivefold and threefold higher than in controls fed ad libitum. 4. The elevation in liver lipogenesis during re-feeding was greatest on a diet containing 1% of corn oil, whereas in extrahepatic tissues the increase in lipogenesis was greater when the mice were re-fed or were allowed limited access to a diet containing 20% of corn oil. These results suggest that the causes of the increased rate of incorporation of (14)C from [U-(14)C]glucose into fatty acids during re-feeding may be different in liver from that in extrahepatic tissues.     

益生菌干预对高脂高糖饮食诱导肥胖小鼠肠道菌群及脂代谢影响的研究

目的 探讨益生菌干预对高脂高糖饮食诱导肥胖小鼠肠道菌群及脂代谢的影响。方法 C57BL/6J雌性小鼠30只随机分为正常对照组、肥胖组和益生菌干预组,每组10只,分别给予标准饲料、高脂高糖饲料以及高脂高糖饲料同时给予益生菌干预,连续喂养6周,测量并分析三组小鼠的体重。留取小鼠粪便样本,应用PCR-DGGE法分析菌群,应用酶反应比色法分析三组小鼠血脂情况。结果 与正常对照组小鼠相比,肥胖小鼠体重明显增加,益生菌干预组小鼠体重略有增加;肥胖组小鼠肠道菌群紊乱,与正常对照组分别聚为两大类,益生菌干预组小鼠肠道菌群与正常对照组聚为一大类。肥胖小鼠血清总胆固醇、低密度脂蛋白含量升高,益生菌干预组小鼠较肥胖组血清总胆固醇、低密度脂蛋白含量降低,但与正常对照组仍有差异。结论 高脂高糖饮食诱导肥胖小鼠存在肠道菌群结构失调及脂代谢异常,益生菌干预可以改善肥胖小鼠菌群失调以及脂代谢紊乱。     

Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine

We studied the effect of dietary fat type, varying in polyunsaturated-to-saturated fatty acid ratios (P/S), on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1), or safflower oil (HF-SO; P/S 7.8) for 8 wk. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared with the HF-OO, HF-SO, or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes-to-Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.     

葛仙米多糖对高脂小鼠血脂和肠道微生物的影响

[目的]研究葛仙米多糖对高脂饲料喂养小鼠血脂和肠道微生物的影响.[方法]将健康的8周龄雄性小鼠分成5组,每组10只:正常组C57/6CNC小鼠(N:灌胃生理盐水,喂饲标准饲料),对照组ApoE-/-小鼠(C:灌胃生理盐水,喂饲标准饲料),模型组ApoE-/-小鼠(M:灌胃生理盐水,喂饲高脂高胆固醇饲料),葛仙米多糖低剂...     

The number of x chromosomes causes sex differences in adiposity in mice

Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones. Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the "four core genotypes," to distinguish between effects of gonadal sex (testes or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal male and female mice carrying XX or XY sex chromosome complements. Mice were gonadectomized to remove the acute effects of gonadal hormones and to uncover effects of sex chromosome complement on obesity. Mice with XX sex chromosomes (relative to XY), regardless of their type of gonad, had up to 2-fold increased adiposity and greater food intake during daylight hours, when mice are normally inactive. Mice with two X chromosomes also had accelerated weight gain on a high fat diet and developed fatty liver and elevated lipid and insulin levels. Further genetic studies with mice carrying XO and XXY chromosome complements revealed that the differences between XX and XY mice are attributable to dosage of the X chromosome, rather than effects of the Y chromosome. A subset of genes that escape X chromosome inactivation exhibited higher expression levels in adipose tissue and liver of XX compared to XY mice, and may contribute to the sex differences in obesity. Overall, our study is the first to identify sex chromosome complement, a factor distinguishing all male and female cells, as a cause of sex differences in obesity and metabolism.