饮食诱导肥胖易感和肥胖抵抗大鼠HSL和LPL基因表达的研究

目的探讨高脂饮食诱导肥胖易感(OP)大鼠和肥胖抵抗(OR)大鼠,激素敏感性脂肪酶(HSL)和脂蛋白脂肪酶(LPL)基因表达的差别。方法健康雄性SD大鼠80只,高脂饲料喂饲5周后,筛选出OP大鼠和OR大鼠,再将所有大鼠转为基础饲料喂饲10周后,处死动物,收集血清和白色脂肪组织,应用RT-PCR方法比较白色脂肪组织HSL和LPL基因的表达。结果高脂饲料喂饲5周后,OP大鼠白色脂肪组织HSL基因表达显著低于OR大鼠,而LPL基因表达显著高于OR大鼠;而转成基础饲料喂饲10后,OP大鼠HSL基因表达与OR大鼠无显著差异,但LPL基因表达仍显著高于OR大鼠。结论HSL基因表达水平下降和LPL基因表达水平升高,通过抑制脂肪分解促进脂肪合成,导致高脂饮食诱导肥胖易感大鼠的形成。HSL基因高表达更多是由高脂饮食诱导产生的,而LPL基因表达升高才是肥胖大鼠的特征性基因表达改变。     

体外快速减肥模型的建立及初步评价

目的建立一种快速、高效的减肥药物体外筛选模型,并对该模型进行初步评价。方法用油酸诱导SD大鼠原代成熟脂肪细胞建立肥胖细胞模型,选用阳性药物异丙肾上腺素和已明确有减肥作用的功能因子染料木素、咖啡因及阴性对照物姜黄素对该肥胖模型进行评价。结果试验所选用的阳性受试物均能显著刺激脂肪细胞发生脂解,而阴性受试物无脂解作用。结论该模型可以用于减肥药物的体外快速筛选。     

儿茶素和咖啡碱组合对3T3-L1细胞增殖及脂肪代谢的影响

目的研究对儿茶素和咖啡碱对3T3-L1细胞的增殖及脂肪代谢的影响。方法采用四甲基偶氮唑盐比色法(MTT)检测对3T3-L1细胞增殖的影响;3T3-L1细胞诱导分化8d后,对各组细胞进行油红O染色并测定细胞内甘油三酯(TG)含量;细胞分化12d后,添加儿茶素和咖啡碱组合或同时添加去甲肾上腺素(NA)作用24h,分析各组细胞内脂肪分解。结果儿茶素能明显抑制3T3-L1细胞的增殖;儿茶素和咖啡碱组合能明显抑制3T3-L1细胞分化后,细胞内TG的沉积,且在相同儿茶素浓度下,咖啡碱浓度越高抑制效果越明显。咖啡碱明显提高NA诱导成熟脂肪细胞脂解的能力,且呈剂量效应关系。结论儿茶素和咖啡碱组合能够抑制脂肪细胞增殖和甘油三酯积聚,咖啡碱促进激素诱导脂肪细胞中脂肪分解。     

绿茶和红茶多酚对大鼠脂肪分化相关基因表达影响的比较研究

目的:比较绿茶多酚(GTP)和红茶多酚(BTP)抗肥胖作用及其分子机制。方法:将实验大鼠分为空白对照组,高脂饲料+GTP组,高脂饲料+BTP组,高脂饲料组,定期检测体重,喂饲3个月后,观察脂肪组织和血脂水平变化,并提取附睾脂肪组织,应用RT-PCR技术观察与脂肪细胞分化相关的基因pref-1,aP2,TNF-α,瘦素,PPAR-γ,C/EBP-α在mRNA水平的表达。结果:GTP和BTP均能明显降低体重,减少脂肪。同时,GTP和BTP均能显著地抑制脂肪细胞特殊标记物aP2,TNF-α,瘦素,但两者之间无统计学差异。此外,GTP还上调前脂肪细胞标记物pref-1,且下调转录因子PPAR-γ。结论:GTP和BTP均可通过调节与脂肪细胞分化相关的基因,逆转脂肪细胞的分化,达到抗肥胖的作用,且GTP抗肥胖作用强于BTP。     

锌-α2-糖蛋白在肿瘤恶病质脂肪代谢中的作用

锌-α2-糖蛋白（ZAG）是一种新型脂肪细胞因子,主要通过促进脂肪分解和利用来减少体内脂肪含量,在肿瘤恶病质的发生中发挥重要作用.ZAG促进脂肪分解的作用主要是通过增强激素敏感性脂酶活性、激活细胞膜上β3肾上腺素受体,进而上调细胞内环腺苷酸信号转导途径完成的.此外,ZAG能促进脂联素,抑制瘦素在脂肪细胞和脂肪组织中的表达.脂肪细胞中ZAG的表达受糖皮质激素、过氧化物酶体增殖物激活受体γ激动剂罗格列酮、肿瘤坏死因子-α等多种因素的调节.ZAG有作为肿瘤标志物的潜在价值,有望成为肿瘤恶病质治疗新的靶点.     

乌龙茶水浸物对大鼠的减肥作用

[目的]探讨乌龙茶的减肥作用。[方法]选用SD雄性大鼠用高能量高脂肪饲料制备肥胖模型大鼠后,选择其中32只模型鼠,随机分为肥胖对照组、低、中、高剂量组,分别灌服蒸馏水、0.4g/kg.bw、1.2g/kg.bw、2.4g/kg.bw的乌龙茶水浸物30d后,测定体重、体脂及脂肪细胞最大径。[结果]30d后,灌服中、高剂量乌龙茶水浸物的大鼠体重、体重增加、体围、腹膜后与附睾周脂肪组织重量及脂肪系数、附睾周与肩胛间脂肪细胞的最大径明显低于肥胖对照组大鼠,而饲料总摄取量在各组间却无明显差异。中剂量大鼠腹膜后、肾周脂肪系数也明显低于低剂量组大鼠。[结论]乌龙茶具有减肥作用,中剂量可能为适宜剂量。     

乌龙茶与绿茶减肥效果的比较研究

目的：比较乌龙茶与绿茶的减肥效果。方法：56只雄性SD大鼠随机分为4组,其中3组以高能量高脂肪饲料喂饲大鼠,同时分别予以蒸馏水或乌龙茶、绿茶1．2g／kg.bw。另1组喂以基础饲料,连续喂养30天后,测定大鼠体重、体围、肝脏重量、附睾周、肾周及肩胛间脂肪组织重量,计算Lee‘s指数、肝重／体重、脂肪重／体重,并测定血脂、下丘脑神经递质(去甲肾上腺素)含量。结果：与高脂对照组比较,乌龙茶与绿茶组大鼠体重、增重、附睾周与肾周脂肪组织重量、肾周脂肪重／体重、血清甘油三酯含量明显较低,绿茶组大鼠体围也较低,而两组间无明显差异。结论：乌龙茶与绿茶均有减肥效果,且在相同剂量下两者减肥效果相似。     

几丁聚糖对大鼠体重的影响及与体内瘦素和睾酮关系的研究

目的：为探讨几丁聚糖（chitosan)对大鼠体重的影响及其与体内瘦素和睾酮的关系。方法：给5组大鼠分别喂饲基础饲料，高脂饲料和加不同剂量chitosan的高脂饲料共7周，每周称1次体重，于第7周末断头取血，用放射免疫试剂盒检测血浆中瘦素和血清中酮，结果：chitosan具有明显抑制高脂饲料诱导大鼠肥胖和降低血中睾酮的作用，通过体重与瘦素变化规律的分析，推测chitosan可能对瘦素的分泌具有促进作用。结论：chitosan降低血中睾酮浓度，从而促进瘦素分泌，可能是chitosan抑制高脂饲料诱导大鼠脂胖的部分原因。     

断乳后不同剂量铁强化膳食对大鼠成年期肥胖诱导后瘦素水平的影响

目的:研究断乳大鼠铁强化膳食对其成年高脂膳食诱导肥胖后血清瘦素水平的影响。方法:将85只初断乳雄性SD大鼠随机分为基础饲料组和高(4倍)、中(3倍)、低(2倍)剂量铁强化组。4周后各组均以基础饲料喂养1周,于第5周末测定大鼠体脂和血清瘦素含量。将基础饲料组16只大鼠随机分为正常对照组和肥胖诱导组,肥胖诱导组和3个铁强化组均喂以高脂饲料。高脂干预8周后处死所有大鼠计算脂/体比,检测血清瘦素含量。结果:高脂干预后,肥胖诱导组体重、体脂含量、瘦素水平均高于其他各组,3个铁强化组瘦素含量高于正常对照组。结论:生命早期适量补铁能够促进大鼠成年期肥胖诱导后的脂肪分解,维持大鼠体重平衡,保证机体瘦素分泌及功能正常。     

瘦素抵抗肥胖大鼠脂肪组织SOCS-3、PPARγ及ACO mRNA水平的探讨

目的观察高脂饮食诱导的肥胖瘦素抵抗大鼠细胞因子信号转导抑制因子-3(SOCS-3)、过氧化物酶体增殖物激活受体γ(PPARγ)及乙酰辅酶A氧化酶(ACO)mRNA表达水平的变化。方法30只Wistar雄性大鼠,6只为对照组喂饲基础饲料,24只为高脂组喂饲高脂饲料,第8周末按体重增量从高脂组中筛选出8只大鼠作为肥胖组,测定对照组和肥胖组大鼠血清瘦素,附睾脂肪组织中SOCS-3,PPARγ以及ACO mRNA表达。结果肥胖组大鼠体重以及血清瘦素水平均显著高于对照组(P<0.05);肥胖组脂肪组织SOCS-3、PPARγ mRNA水平显著高于对照组(P<0.05),而ACO mRNA则显著低于对照组(P<0.05)。结论高脂饮食诱导的肥胖大鼠存在瘦素信号转导通路的抑制,脂肪酸氧化能力降低,脂肪合成能力增强。     

Platycodi radix affects lipid metabolism in mice with high fat diet-induced obesity

An aqueous extract of Platycodi radix inhibited the hydrolysis of triolein emulsified with phosphatidylcholine by pancreatic lipase in vitro and it reduced the elevation of rat plasma triacylglycerol level 2-4 h after oral administration of a lipid emulsion containing corn oil. These preliminary results suggested that the aqueous extract of Platycodi radix may inhibit the intestinal absorption of dietary fat by inhibiting its hydrolysis. Therefore, we examined the antiobesity activity of the aqueous extract of Platycodi radix by testing whether the extract prevented the obesity induced by feeding a high fat diet to mice for 8 wk. Body weights at 3-8 wk and the final parametrial adipose tissue weights were significantly lower in mice fed the high fat diet containing 5% aqueous extract of Platycodi radix than in the controls fed the high fat diet. The aqueous extract of Platycodi radix also significantly reduced hepatic triacylglycerol concentrations that were elevated in mice fed the high fat diet alone. Inulin, which is a major component of Platycodi radix, had no effect on the hydrolysis of triolein emulsified with phosphatidylcholine by pancreatic lipase in vitro, and did not prevent obesity or the fatty liver induced by the high fat diet. On the other hand, the total saponin fraction of the aqueous extract inhibited pancreatic lipase activity in vitro. Therefore, the antiobesity effect of the aqueous extract of Platycodi radix in mice fed a high fat diet may be due in part to the inhibition of intestinal absorption of dietary fat by the saponins of Platycodi radix.     

Saponins from platycodi radix ameliorate high fat diet-induced obesity in mice

We examined the effects of crude saponins isolated from Platycodi radix on the degree on fat storage induced in mice by feeding a high fat diet for 9 wk. We reported previously that feeding mice a high fat diet for a longer time caused obesity and fatty liver compared with those fed a low fat diet, nonpurified diet. Feeding a high fat diet containing 10 or 30 g/kg crude saponins prevented the body and parametrial adipose tissue weight increases and hepatic steatosis of mice fed the high fat diet alone. Furthermore, crude saponins (375 mg/kg) inhibited the elevations in blood triacylglycerol in rats orally administered a lipid emulsion compared with that of rats given the lipid emulsion alone. Previously, we reported that crude saponins inhibited pancreatic lipase activity in vitro. To identify the active substance(s) of crude saponins, we examined the effects of purified platycodin D, the primary saponin in the crude mixture, on pancreatic lipase activity and on the blood triacylglycerol elevation in rats administered the oral lipid emulsion tolerance test. Platycodin D (0.5 and 1.0 g/L) inhibited pancreatic lipase activity in vitro and at a dose of 244 mg/kg, inhibited the elevation of blood triacylglycerol. Therefore, the antiobesity effect of the crude saponins in mice fed a high fat diet may be due to the inhibition of intestinal absorption of dietary fat by platycodin D.     

La digestion des graisses : des aspects moléculaires à la pathologie

Obesity is a severe public health problem in industrialised as well in emergent countries. Considering that dietary fat, because of its high calorific value, plays an important role in the development of obesity, reduction of fat digestion through pancreatic lipase inhibition is now considered as a novel approach in obesity treatment. The isolated C-terminal domain of pancreatic lipase acting as a “protein lure” toward colipase offers a new way for inhibiting intestinal lipolysis by competing with lipase for colipase. In this respect, the C-terminal domain is a very specific inhibitor of pancreatic lipase, compared to the leading obesity drug, orlistat which inhibits the various lipases of the digestive tract. Administration of C-terminal domain to rats fed a high fat diet reduces diet-induced body weight gain and induces an amelioration of fatty liver. Therefore, the C-terminal domain is a strong candidate for an agent that impedes intestinal absorption of dietary fat by inhibiting specifically pancreatic lipase activity.     

Inhibitory effects of grape seed extract on lipases

OBJECTIVE: The aim of the present study was to assess the effects of grape seed extract (GSE) on the fat-metabolizing enzymes pancreatic lipase, lipoprotein lipase, and hormone-sensitive lipase in vitro and evaluate its potential application as a treatment for obesity. METHODS: Crushed grape seeds were extracted in ethanol, and the extract was assayed for the measurement of inhibitory effects on pancreatic lipase and lipoprotein lipase activities and on lipolysis of 3T3-L1 adipocytes. RESULTS: The GSE rich in bioactive phytochemicals showed inhibitory activity on the fat-metabolizing enzymes pancreatic lipase and lipoprotein lipase, thus suggesting that GSE might be useful as a treatment to limit dietary fat absorption and the accumulation of fat in adipose tissue. The observed reduction in intracellular lipolytic activity of cultured 3T3-L1 adipocytes may reduce the levels of circulating free fatty acids that have been linked to insulin resistance in obese patients. CONCLUSION: The GSE rich in compounds that inhibit lipases may provide a safe, natural, and cost-effective weight control treatment.     

Antiobesity action of a daidzein derivative on male obese mice induced by a high-fat diet

Emerging evidence suggests that consumption or supplementation of foods rich in isoflavones may has a beneficial effect on obesity and glucose levels in animals and humans. It has been demonstrated that genistein, the main component of isoflavones, could significantly reduce body weight and fat pad size. However, there is no evidence as to whether daidzein, which is also a main component of isoflavones, has the same effect. We hypothesize that LRXH609 (Dzd; a daidzein derivative) also has an antiobesity effect. In this study, we investigate the effects of Dzd on body weight, adipose tissue, blood, and liver lipid levels in obese mice fed a high-fat diet. Activities of pancreatic lipase and lipoprotein lipase, as well as lipolysis, were verified to clarify the potential mechanism of the daidzein. The results indicate that Dzd can significantly reduce body and fat pad weight and ameliorate the high-fat diet–induced hyperlipoidemia. We also found that Dzd inhibits the activity of pancreatic lipase and lipoprotein lipase in a dose-dependent manner, inhibits the differentiation of rat preadipocytes, and stimulates lipolysis by activating hormone-sensitive lipase.     

Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men

BACKGROUND: Catechins, the major component of green tea extract, have various physiologic effects. There are few studies, however, on the effects of catechins on body fat reduction in humans. It has been reported that the body mass index (BMI) correlates with the amount of malondialdehyde and thiobarbituric acid-reactive substances in the blood. OBJECTIVE: We investigated the effect of catechins on body fat reduction and the relation between oxidized LDL and body fat variables. DESIGN: After a 2-wk diet run-in period, healthy Japanese men were divided into 2 groups with similar BMI and waist circumference distributions. A 12-wk double-blind study was performed in which the subjects ingested 1 bottle oolong tea/d containing 690 mg catechins (green tea extract group; n = 17) or 1 bottle oolong tea/d containing 22 mg catechins (control group; n = 18). RESULTS: Body weight, BMI, waist circumference, body fat mass, and subcutaneous fat area were significantly lower in the green tea extract group than in the control group. Changes in the concentrations of malondialdehyde-modified LDL were positively associated with changes in body fat mass and total fat area in the green tea extract group. CONCLUSION: Daily consumption of tea containing 690 mg catechins for 12 wk reduced body fat, which suggests that the ingestion of catechins might be useful in the prevention and improvement of lifestyle-related diseases, mainly obesity.     

普洱茶提取物对饮食诱导肥胖大鼠脂质合成相关基因表达的影响

目的观察普洱茶提取物(PTE)对饮食诱导性肥胖大鼠脂质合成相关基因的影响,探讨普洱茶抗肥胖的作用机制。方法30只雄性Sprague-Dawley大鼠随机分为3组(n=10):正常对照组,普通饲料;高脂组,高脂饲料;高脂+PTE组,高脂饲料+PTE。采用高脂饲料建立肥胖大鼠模型,测定大鼠体重和脂肪组织重量,判定减肥效果;采用real-timePCR检测PTE对脂质合成相关基因的表达影响。结果PTE能有效减轻动物体重和脂肪组织重量,显著下调二酰基甘油酰转移酶-1(DGAT1)、固醇辅酶A去饱和酶1(SCD1)和固醇调节元件结合蛋白(SREBP)-1cmRNA的表达。结论PTE可通过调节脂质合成相关基因,减少脂肪的合成,达到预防肥胖的作用。     

Effects of diet and ketones on rat pancreatic lipase in cultured acinar cells

The activity, synthesis rate and mRNA level of pancreatic lipase increase with dietary fat intake. Ketones, intermediates of lipid metabolism, have been proposed to mediate this change. Therefore, we investigated their direct effect on cultured pancreatic acinar cells and examined their possible interactive effects with glucose and dietary fat. beta-Hydroxybutyrate (0.01 to 2 mmol/L) did not affect lipase activity in cells isolated from rats fed a commercial nonpurified (NP) diet and cultured in high glucose (HG, 27.8 mmol/L) or low glucose (LG, 6.9 mmol/L) medium. The effects of ketones were also examined in acinar cells isolated from rats fed purified high fat (HF, 67% of energy from fat) or low fat (LF, 11% of energy from fat) diet. Cellular lipase was significantly higher in cells from HF-fed rats at both 24 and 48 h (264% and 145% of LF values, respectively; P less than 0.0001). beta-Hydroxybutyrate significantly increased (P less than 0.04) lipase activity in LF cells at 48 h but did not affect lipase activity in HF cells. These studies suggest that ketones may be involved in the regulation of pancreatic lipase in rats fed a LF diet, but their role is complex and interactive with dietary carbohydrate and fat.     

Prevention of diet-induced obesity by dietary black tea polyphenols extract in vitro and in vivo

Objective

The effects of certain tea components on the prevention of obesity in humans have recently been reported, although it is still unclear whether black tea consumption is beneficial. We obtained black tea extract (BTPE) consisting of polyphenols specific to black tea, and from it, prepared a polymerized polyphenol fraction (BTP). The effectiveness of oral administration of the BTPE was examined in in vitro and in vivo experiments.

Methods

Effects of BTPE or BTP on pancreatic lipase activity were investigated in vitro. Male Wistar rats were administered an oral lipid emulsion containing BTPE at a concentration of 500 or 1000 mg/kg body weight and sequential plasma lipid levels were measured. Female C57BL/6N mice were fed a standard or high-fat diet supplemented with 1% or 5% (w/w) BTPE for 8 wk and changes in body weight were examined.

Results

BTP and BTPE inhibited pancreatic lipase activity with an IC₅₀ of 15.5 and 36.4 μg/mL in vitro, respectively. BTPE suppressed increases in rat plasma triglyceride levels in a dose-dependent manner after oral administration of a lipid emulsion. Furthermore, administration of the 5% BTPE suppressed increases in body weight (P < 0.05), parametrial adipose tissue mass, and liver lipid content (reduced to 56.9% and 81.7% of control mice, respectively, P < 0.05) in mice fed a high-fat diet.

Conclusion

The BTPE may prevent diet-induced obesity by inhibiting intestinal lipid absorption. It was suggested that the major active component in the BTPE was BTP.